Improving the radical cure of vivax malaria: A multicentre randomised comparison of short and long course primaquine regimens
Lead Research Organisation:
University of Oxford
Department Name: Tropical Medicine
Abstract
Plasmodium vivax malaria is a major cause of morbidity and an important contributor to mortality in poorly resourced endemic areas in Asia, South America and Africa. The greatest burden of vivax malaria is in South and Southeast Asia, where 2.85 billion people are at risk and experience 100 to 300 million cases of vivax malaria each year. Plasmodium vivax causes repetitive febrile illness associated with worsening anaemia particularly in young children and in pregnant women. Severe anaemia and low birth weight resulting in direct and indirect mortality. Despite the very large population affected by vivax malaria and its socioeconomic burden, it has been and continues to be a neglected disease; global malaria R&D spending on combating P. vivax amounted to just 3% of total spending on malaria between 2007-2009. Since the 1950s chloroquine has been the mainstay of treatment for acute vivax malaria. However resistance to chloroquine was first reported in Papua, Indonesia and there is now good evidence that it is prevalent across the Indonesian archipelago and has spread throughout much of the vivax endemic world.
Unlike Plasmodium falciparum, P. vivax has in addition to the blood stage a liver stage of the parasite (known as hypnozoite) capable of reawakening weeks or even months after the primary infection. The complete treatment of vivax malaria requires administration of antimalarials to eradicate both the blood and liver stages of the parasite. Primaquine remains the only drug on the market for its liver stage activity. However the efficacy of primaquine resistance is difficult to determine due to variable relapsing patterns of P. vivax and the need for prolonged follow up to capture the late relapses. The widespread use of primaquine has been severely limited because of concerns regarding both its efficacy and safety. Primaquine causes haemolysis in patients with G6PD deficiency, an inherited disorder occurring in 5-35% of patients in endemic zones. There a few readily available, affordable and reliable diagnostic tools for the rapid testing of GPD deficiency, and thus clinicians often reluctant to prescribe a therapy that is potentially harmful with limited perceived benefit. When it is prescribed adherence to the currently recommended 14 day treatment regimen is poor.
This proposal aims to provide critical evidence on the use of primaquine, a drug which is being increasingly recognised as a crucial tool in the global fight against malaria. We hypothesise that a shorter course high dose primaquine regimens will provide a practical approach to antirelapse therapy that is safe and effective. Our randomized placebo controlled multicentred trial will compare two different regimens of primaquine against schizontocidal treatment alone in 5 Asian countries. Trial centres will be established in South Asia (India, Pakistan and Afghanistan) where 70% of all cases occur and the interval between vivax relapses is relatively long, as well as two sites from South East Asia (Vietnam and Indonesia) where the interval between relapses is shorter and the risk of relapse greater.
The primary objective will be to compare two primaquine regimens giving the same total dose primaquine over either 7 or 14 days. Patients presenting with pure vivax malaria, meeting the inclusion criteria will be randomly assigned to receive one of the following three treatments:
Option 1 - Standard blood schizontocidal therapy + 14 days of supervised primaquine (7mg/kg total dose).
Option 2 - Standard blood schizontocidal therapy + 7 days of supervised primaquine (7mg/kg total dose).
Option 3 - Standard schizontocidal therapy. Treatment with primaquine will be deferred until the end of the follow up period. This is the control regimen.
Following treatment, patients will be followed for 12 months to monitor the number of vivax recurrences and the level of anaemia. Each recurrence of vivax malaria will be treated with the same allocated regimens.
Unlike Plasmodium falciparum, P. vivax has in addition to the blood stage a liver stage of the parasite (known as hypnozoite) capable of reawakening weeks or even months after the primary infection. The complete treatment of vivax malaria requires administration of antimalarials to eradicate both the blood and liver stages of the parasite. Primaquine remains the only drug on the market for its liver stage activity. However the efficacy of primaquine resistance is difficult to determine due to variable relapsing patterns of P. vivax and the need for prolonged follow up to capture the late relapses. The widespread use of primaquine has been severely limited because of concerns regarding both its efficacy and safety. Primaquine causes haemolysis in patients with G6PD deficiency, an inherited disorder occurring in 5-35% of patients in endemic zones. There a few readily available, affordable and reliable diagnostic tools for the rapid testing of GPD deficiency, and thus clinicians often reluctant to prescribe a therapy that is potentially harmful with limited perceived benefit. When it is prescribed adherence to the currently recommended 14 day treatment regimen is poor.
This proposal aims to provide critical evidence on the use of primaquine, a drug which is being increasingly recognised as a crucial tool in the global fight against malaria. We hypothesise that a shorter course high dose primaquine regimens will provide a practical approach to antirelapse therapy that is safe and effective. Our randomized placebo controlled multicentred trial will compare two different regimens of primaquine against schizontocidal treatment alone in 5 Asian countries. Trial centres will be established in South Asia (India, Pakistan and Afghanistan) where 70% of all cases occur and the interval between vivax relapses is relatively long, as well as two sites from South East Asia (Vietnam and Indonesia) where the interval between relapses is shorter and the risk of relapse greater.
The primary objective will be to compare two primaquine regimens giving the same total dose primaquine over either 7 or 14 days. Patients presenting with pure vivax malaria, meeting the inclusion criteria will be randomly assigned to receive one of the following three treatments:
Option 1 - Standard blood schizontocidal therapy + 14 days of supervised primaquine (7mg/kg total dose).
Option 2 - Standard blood schizontocidal therapy + 7 days of supervised primaquine (7mg/kg total dose).
Option 3 - Standard schizontocidal therapy. Treatment with primaquine will be deferred until the end of the follow up period. This is the control regimen.
Following treatment, patients will be followed for 12 months to monitor the number of vivax recurrences and the level of anaemia. Each recurrence of vivax malaria will be treated with the same allocated regimens.
Technical Summary
This is a multi-centre, open label, three-arm randomised non-inferiority trial to compare two primaquine anti-relapse regimens. The same total dose 7mg primaquine/kg will be given either over 14 or over 7 days. A control arm which receives only schizontocidal therapy without anti-relapse therapy will provide the comparison for safety, tolerability and relapse data.
Once randomised into one treatment arm the subject will receive the same prescribed regimen for subsequent recurrent vivax episodes throughout the 12 months follow-up period.
All potential study participants will be tested for G6PD deficiency. Patients identified as having G6PD deficiency will receive standard blood schizontocidal therapy plus 8 weeks of weekly primaquine dosing (7mg/kg total dose).
Once randomised into one treatment arm the subject will receive the same prescribed regimen for subsequent recurrent vivax episodes throughout the 12 months follow-up period.
All potential study participants will be tested for G6PD deficiency. Patients identified as having G6PD deficiency will receive standard blood schizontocidal therapy plus 8 weeks of weekly primaquine dosing (7mg/kg total dose).
Planned Impact
The primary beneficiaries of the proposed trial are the 2.8 billion people at risk of infection by P. vivax and the 100 to 400 million patients who may be prescribed primaquine therapy against relapse. These patients would receive a regimen of therapy supported by clinical evidence of safety and efficacy, including, possibly, G6PDd patients, pregnant women, and small children now typically excluded from therapy for want of evidence of safety. The economic and societal impacts of these benefits will be diminished burdens of morbidity and mortality caused by this infection that would very likely follow with more aggressive advocacy for the application of primaquine therapy with the confidence of doing so without causing serious harm and with the greater certainty of deriving public health benefit that comes with proven efficacy. In many endemic areas, the successful application of primaquine in a single patient may avert secondary attacks, each attack coming with greater probability of severe illness and a potential for transmission. In short, this trial develops the necessary clinical evidence to support broad attack on the most significant reservoir of P. vivax.
The National Malaria Control Programmes (NMCP) of the countries where this study will take place will be major beneficiaries of the study. Our study seeks both to inform and involve policymakers and stakeholders in the early phase of the study so as to ensure local ownership. We will invite policymakers and stakeholders to planning meetings as early as possible and keep them updated about the progress of the study. On completion of the study, the implications and policy relevance of the results will be discussed with project partners, national policy makers, and representatives of local communities at a stakeholders' meeting. The efficacy and safety of high dose primaquine compared with the control arm will inform countries partners, on the risks and benefits of such a policy. Based on emerging consensus, policy-ready documents will be prepared and disseminated by the partners. It is anticipated that policy impact will occur within 6-12 months of study completion and will result in improved treatment guidelines for the delivery of antirelapse treatment regimens.
At a regional level, the importance of safe and effective radical cure of P. vivax has already been recognized by regional experts as a critical step in the control and elimination of malaria in the Asia-Pacific. Policy recommendations coming from the proposed trial will help develop better malaria control strategies for other Asian countries.
WHO reports and opinions influence regional policymakers. Several of the investigators of the proposed project participate in and on occasion chair WHO technical advisory groups on malaria chemotherapy. In their capacity as technical consultants they will feed back the results of this study not only to rationalise the risk benefits of primaquine therapy, as well as the experience gathered on the optimal study design of subsequent antirelapse studies. The data gathered on the safety of primaquine will inform the use of primaquine for both P. vivax radical cure and also P. falciparum transmission blocking regimens. Thus the evidence developed in this trial will improve the capacity of national malaria control programs to achieve elimination goals.
Research capacity in country research partner institutes will be enhanced by providing both short term and long term training and mentorship for research staff and students. The proposed project will build on existing trials capacity. Collaborative staff in the Mahidol Oxford University research Unit will provide support to write new proposals for research funding for studies beyond the end of the trial. Health worker capacity will be strengthened through training on the administration of antirelapse treatment, improving skills in malaria diagnosis and drug administration.
The National Malaria Control Programmes (NMCP) of the countries where this study will take place will be major beneficiaries of the study. Our study seeks both to inform and involve policymakers and stakeholders in the early phase of the study so as to ensure local ownership. We will invite policymakers and stakeholders to planning meetings as early as possible and keep them updated about the progress of the study. On completion of the study, the implications and policy relevance of the results will be discussed with project partners, national policy makers, and representatives of local communities at a stakeholders' meeting. The efficacy and safety of high dose primaquine compared with the control arm will inform countries partners, on the risks and benefits of such a policy. Based on emerging consensus, policy-ready documents will be prepared and disseminated by the partners. It is anticipated that policy impact will occur within 6-12 months of study completion and will result in improved treatment guidelines for the delivery of antirelapse treatment regimens.
At a regional level, the importance of safe and effective radical cure of P. vivax has already been recognized by regional experts as a critical step in the control and elimination of malaria in the Asia-Pacific. Policy recommendations coming from the proposed trial will help develop better malaria control strategies for other Asian countries.
WHO reports and opinions influence regional policymakers. Several of the investigators of the proposed project participate in and on occasion chair WHO technical advisory groups on malaria chemotherapy. In their capacity as technical consultants they will feed back the results of this study not only to rationalise the risk benefits of primaquine therapy, as well as the experience gathered on the optimal study design of subsequent antirelapse studies. The data gathered on the safety of primaquine will inform the use of primaquine for both P. vivax radical cure and also P. falciparum transmission blocking regimens. Thus the evidence developed in this trial will improve the capacity of national malaria control programs to achieve elimination goals.
Research capacity in country research partner institutes will be enhanced by providing both short term and long term training and mentorship for research staff and students. The proposed project will build on existing trials capacity. Collaborative staff in the Mahidol Oxford University research Unit will provide support to write new proposals for research funding for studies beyond the end of the trial. Health worker capacity will be strengthened through training on the administration of antirelapse treatment, improving skills in malaria diagnosis and drug administration.
Organisations
- University of Oxford (Lead Research Organisation)
- Ethiopian Public Health Institute (Collaboration)
- Wellcome Trust (Collaboration)
- Addis Ababa University (Collaboration)
- Charles Darwin University (CDU) (Collaboration)
- Health Protection and Research Organisation (HPRO) (Collaboration)
- UNIVERSITY OF OXFORD (Collaboration)
- University of Melbourne (Collaboration)
- Eijkman Oxford Clinical Research Unit (Collaboration)
- Health Care and Social Development Organization (Collaboration)
- Bill & Melinda Gates Foundation (Collaboration)
- Government of Indonesia (Collaboration)
- Oxford University Clinical Research Unit (Project Partner)
- University of Indonesia (Project Partner)
- Merlin (Project Partner)
- Society for Applied Studies (Project Partner)
Publications
IMPROV Study Group
(2015)
Improving the radical cure of vivax malaria (IMPROV): a study protocol for a multicentre randomised, placebo-controlled comparison of short and long course primaquine regimens.
in BMC infectious diseases
Cheah PY
(2018)
The ethics of using placebo in randomised controlled trials: a case study of a Plasmodium vivax antirelapse trial.
in BMC medical ethics
Devine A
(2019)
Provider and household costs of Plasmodium vivax malaria episodes: a multicountry comparative analysis of primary trial data.
in Bulletin of the World Health Organization
Rosenthal PJ
(2019)
A shorter course for anti-relapse therapy against vivax malaria.
in Lancet (London, England)
Taylor WRJ
(2019)
Short-course primaquine for the radical cure of Plasmodium vivax malaria: a multicentre, randomised, placebo-controlled non-inferiority trial.
in Lancet (London, England)
Price RN
(2020)
Primaquine for Plasmodium vivax malaria treatment - Authors' reply.
in Lancet (London, England)
Degaga T
(2020)
Disseminating clinical study results to trial participants in Ethiopia: insights and lessons learned
in Malaria Journal
Devine A
(2021)
Global economic costs due to vivax malaria and the potential impact of its radical cure: A modelling study.
in PLoS medicine
Taylor WRJ
(2023)
Weekly primaquine for radical cure of patients with Plasmodium vivax malaria and glucose-6-phosphate dehydrogenase deficiency.
in PLoS neglected tropical diseases
Devine A
(2020)
Cost-Effectiveness Analysis of Sex-Stratified Plasmodium vivax Treatment Strategies Using Available G6PD Diagnostics to Accelerate Access to Radical Cure.
in The American journal of tropical medicine and hygiene
Description | Indonesian policy makers at the Ministry of Health |
Geographic Reach | Asia |
Policy Influence Type | Contribution to a national consultation/review |
Impact | Indonesian policy makers at the Ministry of Health, Centre for Disease Control and local Dinas Kesahatan are particularly interested in our studies. In March 2020, Indonesian PIs took part in a meeting with national policy makers regarding the strategic planning of malaria control and elimination in Indonesia. This meeting has set some key priorities for research agenda that have been set by local partners. Our primary Indonesian collaborator Dr Rini Poespoprodjo, has been invited to several meetings to present her findings on the use of ACTs in pregnancy. The interest in PQ7 (short course primaquine) now added as a national priority for implementation studies |
Description | PNG policy makers at the Ministry of Health |
Geographic Reach | Australia |
Policy Influence Type | Contribution to a national consultation/review |
Impact | PNG currently uses low dose primaquine without G6PD testing. The results of the IMPROV trial show excellent efficacy with high dose short course primaquine. Feasibility studies now underway in PNG to assess whether this novel strategy can be used to change policy. |
Description | Effectiveness of novel approaches to radical cure of vivax malaria |
Amount | $1,599,228 (AUD) |
Funding ID | 1182950 |
Organisation | National Health and Medical Research Council |
Sector | Public |
Country | Australia |
Start | 01/2020 |
End | 12/2025 |
Description | Investigator Award |
Amount | $2,897,046 (AUD) |
Funding ID | GNT2008501 |
Organisation | Menzies School of Health Research |
Sector | Academic/University |
Country | Australia |
Start | 01/2022 |
End | 12/2027 |
Description | Project Grant |
Amount | $4,983,645 (USD) |
Funding ID | OPP1054404 |
Organisation | Bill and Melinda Gates Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 01/2013 |
End | 12/2019 |
Description | Project Grant |
Amount | £2,591,319 (GBP) |
Funding ID | MR/K007424/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2013 |
End | 12/2016 |
Description | Safe and Effective P. vivax Radical Cure (SEPRA) |
Amount | $525,000 (USD) |
Funding ID | INV-024389 |
Organisation | Bill and Melinda Gates Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 11/2020 |
End | 12/2023 |
Description | Wellcome Trust Senior Research Fellowship in Clinical Science |
Amount | £1,406,829 (GBP) |
Funding ID | 200909/Z/16/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2016 |
End | 08/2021 |
Title | Better methods for costing costs of P. vivax malaria |
Description | Analysis from IMPROV data to define costs of malaria episodes. Paper "Provider and household costs of Plasmodium vivax malaria episodes: a multicountry comparative analysis of primary trial data" Bulletin of WHO, 97(12):828-836, 2019. |
Type Of Material | Physiological assessment or outcome measure |
Year Produced | 2019 |
Provided To Others? | Yes |
Impact | Framework for analyses of cost effectiveness of novel strategies for Pvivax radical cure |
Title | Ethical Dilemma of the use of Placebo in primaquine trials |
Description | The IMPROV study presents an ethical dilemma regarding the use of placebo in patients who could be prescribed Primaquine radical cure. Our team has explored these issues and presented a review of the challenges. (BMC Medical Ethics 2018). |
Type Of Material | Improvements to research infrastructure |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | Cheah et al. The ethics of using placebo in randomised controlled trials: a case study of a Plasmodium vivax antirelapse trial. BMC Medical Ethics, in Press 2018. We believe that the use of placebo is justified and indeed necessary if the trials results are to be informative. |
Title | Database of provider and patient cost data generated by the IMPROV study. |
Description | An analysis of provider and patient cost data generated by the IMPROV study. These data are summarised and provided open access in a paper Devine et al . Provider and household costs of Plasmodium vivax malaria episodes: a multicountry comparative analysis of primary trial data. Bulletin of WHO, 97(12):828-836, 2019. |
Type Of Material | Database/Collection of data |
Year Produced | 2019 |
Provided To Others? | Yes |
Impact | The cost data for patient and provdiers for P. vivax malaria represent the most comprehensive data available to date and will underpin future analyses of the global burden of vivax malaria and the cost effectiveness not only of G6PD testing and short course primaquine but many other proposed interventions. |
URL | http://dx.doi.org/10.2471/BLT.18.226688 |
Description | Addis Ababa University |
Organisation | Addis Ababa University |
Country | Ethiopia |
Sector | Academic/University |
PI Contribution | Addis Ababa University is conducting the trial at a site in Arba Minch, Ethiopia |
Collaborator Contribution | Addis Ababa University is conducting the trial at a site in Arba Minch, Ethiopia |
Impact | Keys partners in antimalarial clinical trials conducted in Arba Minch (southern Ethiopia). Including IMPROV, PRIMA and EFFORT. All exploring high dose short course primaquine |
Start Year | 2016 |
Description | Bill and Melinda Gates Foundation |
Organisation | Bill and Melinda Gates Foundation |
Country | United States |
Sector | Charity/Non Profit |
PI Contribution | The BMGF are funding OPRA which is linked to the IMPROV funding stream. |
Collaborator Contribution | The BMGF are funding OPRA which is linked to the IMPROV funding stream. |
Impact | Publications and conference presentations. Research ongoing. |
Start Year | 2012 |
Description | EOCRU |
Organisation | Eijkman Oxford Clinical Research Unit |
Country | Indonesia |
Sector | Hospitals |
PI Contribution | EOCRU are conducting the IMPROV clinical trial at a site in North Sumatra |
Collaborator Contribution | EOCRU are conducting the IMPROV clinical trial at a site in North Sumatra |
Impact | Publication of the trial protocol. Trial follow ups have just finished and data analysis will commence soon once all data has been cleaned. Attendance and presentation at the international meeting of the Asia Pacific Malaria Elimination Network (APMEN) in October 2017. |
Start Year | 2014 |
Description | EPHI |
Organisation | Ethiopian Public Health Institute |
Country | Ethiopia |
Sector | Public |
PI Contribution | EPHI are conducting the trial at a site in Metehara, Ethiopia |
Collaborator Contribution | EPHI are conducting the trial at a site in Metehara, Ethiopia |
Impact | Several large clinical trials including the IMPROV Study and Abreha et al. We continue to work closely with EPHI on trials informing national antimalarial policy. |
Start Year | 2016 |
Description | Eijkman Institute of Molecular Biology |
Organisation | Government of Indonesia |
Country | Indonesia |
Sector | Public |
PI Contribution | I am working with Kevin Baird at the Eijkman Institute of Molecular Biology in Jakarta on antirelapse clinical efficacy trials for short course high dose primaquine. I am also working with Dr Rintis Noviyanti on molecular genotyping of P. vivax. |
Collaborator Contribution | N/A |
Impact | About 2-4 publications per year |
Start Year | 2011 |
Description | Eijkman Oxford Clinical Research Unit |
Organisation | University of Oxford |
Department | Oxford University Clinical Research Unit Vietnam (OUCRU) |
Country | Viet Nam |
Sector | Academic/University |
PI Contribution | EOUCRU are conducting the clinical trial at the South Sumatra site |
Collaborator Contribution | EOUCRU are conducting the clinical trial at the South Sumatra site |
Impact | Kevin Baird and EOUCRU in Jakarta, continue to be active collaborators on clinical trials and individual patient data metanalyses. |
Start Year | 2014 |
Description | HPRO |
Organisation | Health Protection and Research Organisation (HPRO) |
Country | Afghanistan |
Sector | Public |
PI Contribution | HPRO are conducting the trial at one of the sites in Afghanistan |
Collaborator Contribution | HPRO are conducting the trial at one of the sites in Afghanistan |
Impact | Partners conducting IMPROV study in Afghanistan. Ongoing collaborations writing up subprojects on safety and G6PDd |
Start Year | 2013 |
Description | HSDO |
Organisation | Health Care and Social Development Organization |
Country | Uganda |
Sector | Charity/Non Profit |
PI Contribution | HSDO are conducting the clinical trial at one of the sites in Afghanistan. |
Collaborator Contribution | HSDO are conducting the clinical trial at one of the sites in Afghanistan. |
Impact | Partners conducting IMPROV study in Afghanistan. Ongoing collaborations writing up subprojects on safety and G6PD deficiency |
Start Year | 2013 |
Description | IMPROV OPRA |
Organisation | Charles Darwin University (CDU) |
Country | Australia |
Sector | Academic/University |
PI Contribution | Linked to the IMPROV funding stream. IMPROV is delivered through Oxford and OPRA through Menzies School of Health Research. |
Collaborator Contribution | Linked to the IMPROV funding stream. IMPROV is delivered through Oxford and OPRA through Menzies School of Health Research. |
Impact | TBC |
Start Year | 2013 |
Description | IMPROV Study |
Organisation | Wellcome Trust |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | I am working with Professor Day and White on the delivery of the IMPROV study and connected auxiliary studies. |
Collaborator Contribution | MORU are providing clinical trials and laboratory support for conducting the multicentred IMPROV study. |
Impact | TBC |
Description | Mahidol-Oxford Tropical Medicine Research Unit (MORU) |
Organisation | Wellcome Trust |
Department | Mahidol University-Oxford Tropical Medicine Research Programme |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Collaborating on IMPROV and OPRA projects |
Collaborator Contribution | Collaborating on IMPROV and OPRA projects |
Impact | Publications, conference presentations. Ongoing research. |
Start Year | 2011 |
Description | University of Melbourne |
Organisation | University of Melbourne |
Country | Australia |
Sector | Academic/University |
PI Contribution | The team at the University of Melbourne is assisting with the Statistical Plan and statistical analysis for the IMPROV trial. |
Collaborator Contribution | The team at the University of Melbourne is assisting with the Statistical Plan and statistical analysis for the IMPROV trial. |
Impact | The team works on the statistical analysis for malaria clinical trials and metanalyses |
Start Year | 2014 |
Title | Effectiveness of novel approaches to radical cure with tafenoquine and primaquine |
Description | IMPROV Study highlighted that 7 day primaquine was equivalnce to 14 days regimen, but will it has superior effectiveness. The EFFORT Trial has been funded by NHMRC to explore this and also compare to single dose of tafenoquine. Study underway in Bangladesh, Ethiopia, Indonesia and Pakistan. |
Type | Therapeutic Intervention - Drug |
Current Stage Of Development | Late clinical evaluation |
Year Development Stage Completed | 2022 |
Development Status | Under active development/distribution |
Clinical Trial? | Yes |
Impact | The ongoing study, initiated after IMPROV study, will explore safety of PQ7 and whether it offers better effectiveness over current standard of care. If confirmed this trial is set to change national and international policy |
URL | https://www.menzies.edu.au/page/Research/Projects/Malaria/EFFORT_clinical_trial_Effectiveness_of_taf... |
Title | PRIMA study exploring the role of radical cure for patients with P. falciparim |
Description | Pooled analyses have shown a high risk of Pvivax after Pfalciparum, this is a major cause of recurrence and ongoing transmission. A large cluster study in Papua (TRIPI funded by Wellcome Fellowship) showed benefits of universal radical cure to all patients with malaria. (Poespoprodjo et al Lancet ID 2022 doi: 10.1016/S1473-3099(21)00358-3) THe PRIMA study follows in from TRIPI and IMPROV, exploring high dose short course primaquine vs single dose pq for patients with P.falciparum Funded by Australian Academy of Science and Bill Melinda Gates FOundation. |
Type | Therapeutic Intervention - Drug |
Current Stage Of Development | Late clinical evaluation |
Year Development Stage Completed | 2022 |
Development Status | Under active development/distribution |
Clinical Trial? | Yes |
Impact | This novel trial offers a potential paradigm shift in the treatment of malaria. Targeting the hidden reservoir of Pvivax hypnzoites in patients presenting with Pfalciparum. |
URL | https://www.menzies.edu.au/page/Research/Projects/Malaria/PRIMA_clinical_trial_Universal_Radical_Cur... |
Description | ACREME - Webinar. 11th June 2020 Presentation by Kamala Thriemer |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Australian Centre of Research Excellence. Webinar presentation on "Clinical trials to improve radical cure of vivax malaria". To highlight follow on studies from IMPROV study |
Year(s) Of Engagement Activity | 2020 |
Description | APMEN TechTalks Webinar |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Workshop for the Asia Pacific Malaria Elimination Network on "Optimizing radical cure for vivax malaria: Informing policy and practice" by RN Price |
Year(s) Of Engagement Activity | 2021 |
Description | APMEN Vivax Working Group (VxWG) meeting in Kathmandu - 2019 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | The Asia Pacific Malaria Elimination Network conducted a 3 day meeting attended by representative of the National Malaria Control Programs (NMCPs) of 18 malaria endemic countries to discuss how to achieve radical cure of P. vivax. A day long workshop was conducted during which country partners discussed the IMPROV results and what further evidence was needed for policy change. |
Year(s) Of Engagement Activity | 2019 |
Description | APMEN Webinar |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | A webinar on 3rd July 2020 "Optimizing radical cure for vivax malaria: Informing policy and practice". Attended by researchers, national malaria control porgrams and policy makers. Presentations on alternative strategies for radical cure including short course high dose primaquine. |
Year(s) Of Engagement Activity | 2020 |
Description | American Society of Tropical Medicine 68th Annual Meeting - Special Symposium - Nov 2019 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | A talk by RN Price entitled "Optimizing Radical Cure of Vivax Malaria in the Era of Tafenoquine". Highlighting issues of adherence and high efficacy of 7 days primaquine |
Year(s) Of Engagement Activity | 2019 |
Description | Ethiopian stakeholder meeting |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | An Ethiopian stakeholder meeting was convened in November 2019. To present the results of IMPROV study. It was attanded by representatives from the NMCP, the Technical Advisory Group, WHO, Malaria Consortium, PATH, Addis Continental Institute of Public Health, and the Ethiopian Public Health Institute |
Year(s) Of Engagement Activity | 2019 |
Description | Forum on Operational Research in the Context of the Last Mile of Malaria Elimination in GMS Countries - 24th Nov 2020 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Virtual Meeting 24-25 November 2020. RN Price presentation of "Effectiveness of novel approaches to radical cure with tafenoquine and primaquine" |
Year(s) Of Engagement Activity | 2020 |
Description | IMPROV Investigator Meeting |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | The Principal Investigator, Site investigators, Trial Management Group, and analysis team of the IMPROV study met over 2 days in Bangkok, Thailand to report on field site experiences, discuss the results of the primary analysis, make a plan for the main publication and discuss subprojects. This was followed by a 2-day meeting of the main investigators, clinical and analysis team to draft the main manuscript. |
Year(s) Of Engagement Activity | 2018 |
Description | Indonesian Webinar - Parasitic Diseases Control Association. Future Research on Malaria - 2020 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | An Indonesian webinar series. August 19th, 2020. Jakarta, Indonesia. Invtation to speak about "Challenges in Vivax Malaria Elimination in Indonesia" including issues of adherence and short course primaquine regimens. |
Year(s) Of Engagement Activity | 2020 |
Description | Indonesian National Malaria Expert Committee - 2019 |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | Two site investigators from Indonesia attended the National Expert Malaria committee, where IMPROV results were presented and discussed. Indonesia NMCP is now considering feasibility studies to explore the use of G6PD testing and short course primaquine. |
Year(s) Of Engagement Activity | 2019 |
Description | Indonesian Workshop - Promoting the safe radical cure of P. vivax. 2016 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The IMPROV research protocols and issues being addressed on the use of primaquine have been raised at two international meetings of the Asia Pacific Malaria Elimination Network (APMEN). The Vivax Working Group includes representatives of the National Malaria Control Programs of 18 malaria endemic countries, as well as policy makers, healthcare workers, researchers, public private partnerships, industry and other complementary networks.is included a workshop. |
Year(s) Of Engagement Activity | 2016 |
Description | Indonesian Workshop - Tackling Effective Radical Cure of P. vivax. 2017 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The IMPROV research protocols and issues being addressed on the use of primaquine have been raised at two international meetings of the Asia Pacific Malaria Elimination Network (APMEN). The Vivax Working Group includes representatives of the National Malaria Control Programs of 18 malaria endemic countries, as well as policy makers, healthcare workers, researchers, public private partnerships, industry and other complementary networks.is included a workshop. This workshop discussed the principal issues regarding primaquine effectiveness and the need for shorter regimens. |
Year(s) Of Engagement Activity | 2017 |
Description | Joint International Tropical Medicine Meeting (JITMM). - 16th Dec 2020 Presentation by Kamala Thriemer |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | "Improving primaquine treatment for P. vivax malaria" highlighting potential of short course primaquine |
Year(s) Of Engagement Activity | 2020 |
Description | Keystone Conference - Malaria: Confronting Challenges From Drug Discovery to Treatment - 2022 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited speaker Presentation on "Novel approaches for the safe and effective radical cure of P. vivax" by RN Price |
Year(s) Of Engagement Activity | 2022 |
Description | Keystone Symposia Conference on Molecular and Cellular Biology |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | This was a high profile meeting in Addis Ababa with a presentation of the results of IMPROV study to an audience of policy makers and researchers from Across Africa. Highlighted the utility of radical cure and safety of a 7 day regimen. |
Year(s) Of Engagement Activity | 2019 |
Description | Special Symposium of the ASTMH Annual Meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | The IMPROV team presented the results of the IMPROV study at a special symposium of the 67th ASTMH Annual Meeting on November 1, 2018 in New Orleans. |
Year(s) Of Engagement Activity | 2018 |