Clinical Trials in Transfusion Medicine

Lead Research Organisation: MRC Clinical Trials Unit

Abstract

This programme aims to improve current practice in transfusion medicine.|TOPPS|This RCT compares prophylactic vs no prophylactic platelet transfusions and aims to demonstrate that a policy of giving transfusions therapeutically is as clinically effective & safe transfusing prophylactically.|TAPS |This RCT compares pre-operative transfusion vs no transfusion in sickle cell patients undergoing low/medium risk elective surgery & aims to demonstrate that patients who do not have a top-up blood transfusion before an operation, recover just as well as patients who do have a transfusion. |PPIP |This trial aims to corroborate evidence from laboratory studies and show that 7 day platelets (suspended in plasma as well as an alternative suspension) function as well as 5 day platelets.|PRISM|These studies aim to test a blood filter that will remove the prions (proteins) thought to cause vCJD and ensure that the filtered blood is safe when transfused into cardiac surgery patients as well as patients who may require multiple transfusions.|GIN|This non-randomized pilot study aims to assess how safe and effective a new pooled NBS granulocyte product is at preventing and treating sepsis in 30 haemato-oncology patients.

Technical Summary

The aim of the programme of clinical studies in transfusion medicine is to improve evidence base for safe and appropriate use of blood, blood components and alternatives to blood in order to reduce unnecessary exposure to hazards of transfusion, underpin blood service planning for blood component provision, and make best use of a scare donated resource. It is a collaboration between the MRC Clinical Trials Unit and NHS Blood and Transplant, a Special Health Authority with the remit to provide a reliable, efficient supply of blood, organs and associated services to the NHS.|Summary of Studies Currently Open to Recruitment:|TOPPS - Trial of Prophylactic Platelets |Platelet transfusions are given prophylactically to reduce the risk of bleeding in thrombocytopenia. This RCT compares prophylactic vs no prophylactic platelet transfusions in patients with haematological malignancies, & aims to demonstrate that a policy of not giving prophylactic transfusions is not inferior to the standard prophylactic policy, with respect to the proportion of patients developing moderate or severe bleeding.|TAPS - Transfusion Alternatives Pre-operatively in Sickle cell disease |Currently, people with Sickle-cell disease are routinely given a top-up blood transfusion before they undergo surgery in the belief that this helps recovery. However, there is no evidence that this practice is of benefit. This RCT aims to compares pre-operative transfusion vs no transfusion in sickle cell patients undergoing low/medium risk elective surgery. The total number of patients (from the UK and the US) to be recruited to this trial is approximately 400. |PPIP - Platelet Process Improvement Project |The current shelf-life of platelets is 5 days and this short shelf life can cause difficulties with stock control and availability of platelets. As long as no bacterial contamination can be identified, platelet packs can be kept for 7 days. Evidence from laboratory studies show that 7 day platelets function adequately. This trial aims to show that this result is corroborated when platelets are transfused to prevent and treat haemorrhage in thrombocytopenic patients. |PRISM - Trial of Prion-Filtered vs. Standard Red cells in Surgical and Multi-transfused patients |Study A: A non-randomised controlled trial aims to assess the safety of blood that has been passed through a filter to reduce prions (proteins) thought to cause vCJD. |Study B: This double blind RCT that will test the safety of filtered blood in 340 haematology/oncology patients who require regular transfusions for their medical care.

Publications

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Barroso F (2011) Prevalence of maternal anaemia and its predictors: a multi-centre study. in European journal of obstetrics, gynecology, and reproductive biology

 
Description (EASTR) National transfusion policy
Geographic Reach National 
Policy Influence Type Citation in other policy documents
Impact Data on the survival of recipients and donor exposure rates from the EASTR study have been extensively used by modelers at the Department of Health to inform transfusion policy to prevent the secondary spread of variant CJD.
 
Guideline Title Guidelines for the Blood Transfusion Services (8th Edition)
Description (GIN) Component Introduction
Geographic Reach National 
Policy Influence Type Citation in clinical guidelines
Impact The Granulocytes in Neutropenia (GIN) Trial, was an observational study in adults and children receiving the new pooled, whole-blood derived granulocytes in additive solution and plasma component developed by the NHSBT components Laboratory. Results showed that these had a similar safety profile to existing buffy coat sources of granulocytes in neutropenic patients. This led to NHSBT offering pooled granulocytes as a routine component which has the advantages of lower volume, reduced red cell & plasma contamination, and resuspension in male plasma and additive solution to reduce the risk of TRALI, a serious side-effect of transfusion.
URL http://www.transfusionguidelines.org.uk/red-book
 
Description (PPIP) National Transfusion Policy
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact The PPIP trial showed that extended shelf-life (6-7 day old) platelets are safe and do not result in decreased clinical efficacy or an immediate increase in platelet requirements compared to 2-5 day old platelets. In conjunction with the introduction of bacterial testing, it provided the evidence to support the introduction of extended shelf life platelets within the UK, which in turn has led to reduced platelet wastage.
 
Description (PRISM-A) Advisory Committee on the Safety of Blood, Tissues and Organs recommendation
Geographic Reach National 
Policy Influence Type Participation in advisory committee
Impact The PRISM-A safety study demonstrated that transfusion of prion-filtered red cells to surgical patients did not increase the rate of alloimmunisation or transfusion reactions. The study report was accepted by the Department of Health safety committee (SaBTO). PRISM-A results were used by SaBTO in reaching final recommendation on implementation of the P-Capt prion filter to help prevent the spread of vCJD.
 
Guideline Title British Committee for Standards in Haematology guidelines for transfusion in haemoglobinopathy
Description (TAPS) British Committee for Standards in Haematology guidelines
Geographic Reach National 
Policy Influence Type Citation in clinical guidelines
Impact The TAPS trial in adults and children demonstrated that pre-operative transfusions should be offered to sickle cell patients (Hb SS) before undergoing low or medium risk surgery and these results have attracted world -wide interest. Before the trial started clinicians were equally divided in opinion as to whether they should transfuse these patients or not before low or medium risk, and increasingly many low risk patients were not being transfused. The trial results are influencing current practice, and will benefit sickle cell patients given a pre-operative transfusions who will have a reduced chance of developing acute chest syndrome - a serious post-operative complication.
URL http://www.bcshguidelines.com/4_HAEMATOLOGY_GUIDELINES.html
 
Description (TOPPS) National Transfusion Policy
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact The TOPPS trial has demonstrated the overall benefits of continuing to give prophylactic platelets transfusions to blood cancer patients with thrombocytopaenia to reduce the rate of clinically significant bleeding as opposed to "therapeutic-only" platelet transfusions. The results also showed that there is still a high burden of bleeding in many of these patients despite being given prophylactic platelets suggesting that alternative strategies to prevent bleeding should be investigated.
 
Description NHS Blood and Transplant Research and Development (HLA-Epitope)
Amount £352,659 (GBP)
Organisation NHS Blood and Transplant (NHSBT) 
Sector Public
Country United Kingdom
Start 04/2010 
End 03/2014
 
Description NHS Blood and Transplant Research and Development (PROMPT)
Amount £177,751 (GBP)
Organisation NHS Blood and Transplant (NHSBT) 
Sector Public
Country United Kingdom
Start 02/2009 
End 01/2012
 
Description NHS Blood and Transplant Research and Development (Planet 2)
Amount £155,639 (GBP)
Organisation NHS Blood and Transplant (NHSBT) 
Sector Public
Country United Kingdom
Start 04/2010 
End 10/2013
 
Description NHS Blood and Transplant Research and Development (TAPS)
Amount £288,724 (GBP)
Organisation NHS Blood and Transplant (NHSBT) 
Sector Public
Country United Kingdom
Start 09/2007 
End 02/2011
 
Description NHS Blood and Transplant Research and Development (TOPPS)
Amount £367,897 (GBP)
Organisation NHS Blood and Transplant (NHSBT) 
Sector Public
Country United Kingdom
Start 08/2006 
End 12/2011
 
Description NHS Blood and Transplant Research and Development (TRIGGER)
Amount £186,035 (GBP)
Organisation NHS Blood and Transplant (NHSBT) 
Sector Public
Country United Kingdom
Start  
End 03/2013
 
Description NIHR HTA Programme Grant
Amount £1,999,540 (GBP)
Organisation National Institute for Health Research 
Department Health Technology Assessment Programme (HTA)
Sector Public
Country United Kingdom
Start  
End 06/2013
 
Description UK Blood Service (PRISM)
Amount £1,999,999 (GBP)
Organisation Department of Health (DH) 
Sector Public
Country United Kingdom
Start 08/2007 
End 04/2011
 
Title (TOPPS) Standardised method for assessment of bleeding 
Description Tool to standardise the assessment of the frequency and severity of bleeding that can be used as an outcome for the comparison of treatments for patients with bleeding disorders. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2006 
Provided To Others? Yes  
Impact Other groups have adopted the tool for use in their clinical research 
 
Title EASTR 
Description Database of a representative sample of recipients of red cell, platelet and fresh frozen plasma transfusions supplied by the National Blood Service in 2001-02. Information on demography, clinical indications and survival is recorded. 
Type Of Material Biological samples 
Provided To Others? No  
Impact Information not previously available to the National Blood Service, Department of Health and the Advisory Committee on the Safety of Blood, Tissues and Organs 
 
Title EASTR 
Description Database of a representative sample of recipients of red cell, platelet and fresh frozen plasma transfusions supplied by the National Blood Service in 2001-02. Information on demography, clinical indications and survival is recorded. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact Information not previously available to the National Blood Service, Department of Health and the Advisory Committee on the Safety of Blood, Tissues and Organs 
 
Description MRC/NHSBT Clinical Studies Unit 
Organisation NHS Blood and Transplant (NHSBT)
Country United Kingdom 
Sector Public 
PI Contribution The MRC CTU provided expertise in trial design, conduct, data management and analysis to assist NHSBT to develop a programme of clinical trials and related research in transfusion medicine with the aim of improving the evidence base for blood transfusion. In addition to providing the methodological input as well as biostatistians and database management for the studies, the MRC CTU mentored NHSBT staff across all the disciplines involved in the collaboration.
Collaborator Contribution NHSBT provided expertise in blood transfusion and the clinical questions together with resources to conduct the studies.
Impact This collaboration was part of the Division without Portfolio (DWP) programme to support the development of clinical trial expertise and infrastructure in areas in which there was a clinical/public health need. Since 2001, 10 clinical studies have been successfully completed and published in peer reviewed journals. Disciplines involved have included transfusion medicine, epidemiology, biostatistics, data management, trial management. A very important outcome of the collaboration is that it led to the establishment of an independent NHS BT Clinical Trials Unit (see http://www.nhsbt.nhs.uk/clinicaltrialsunit) .
 
Title PPIP 
Description Comparing 6-7day old platelets to 2-5day old platelets - Submitted for publication - Funding from NHSBT 
Type Therapeutic Intervention - Surgery
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2013
Development Status Closed
Clinical Trial? Yes
Impact Extending the shelf-life for platelets to 6-7days will increase product availability, reduce platelet wastage and improve the logistics of supply of platelets to patients. 
URL http://www.isrctn.com/ISRCTN49080246
 
Title PROMPT 
Description Optimisation of platelet donations. Evaluation of clinical outcomes in haemato-oncology patients given platelets from donors whose platelets are at the extreme end of normal activity (e.g. hypo vs hyper reactive when their function is tested in vitro by assessing their responsiveness to 4 different types of platelet agonists). 
Type Therapeutic Intervention - Surgery
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2013
Development Status Under active development/distribution
Clinical Trial? Yes
Impact Awaited 
URL http://www.controlled-trials.com/ISRCTN56366401
 
Title TAPS 
Description BS02/4/RB31 Study hypothesis The trial aims to investigate whether the administration of a blood transfusion preoperatively to patients with sickle cell disease (Hb SS or Hb SB thal) increases or decreases the overall rate of peri-operative complications. - Published - Funding: NHSBT 
Type Therapeutic Intervention - Surgery
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2013
Development Status Closed
Clinical Trial? Yes
Impact Preoperative transfusion was associated with decreased perioperative complications in patients with sickle-cell disease in this trial. This approach could, therefore, be beneficial for patients with the haemoglobin SS subtype who are scheduled to undergo low-risk and medium-risk surgery. 
URL http://www.isrctn.com/ISRCTN00862331
 
Title TOPPS 
Description A randomised controlled trial of prophylactic versus no-prophylactic platelet transfusions in patients with haematological malignancies - Published - Funding: NHSBT 
Type Therapeutic Intervention - Surgery
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2013
Development Status Closed
Clinical Trial? Yes
Impact A strategy of no prophylactic platelet transfusions led to an increased rate of bleeding events of WHO grade 2, 3, or 4, with a significant increase in the number of days with bleeding events of WHO grade 2, 3, or 4. The majority of the bleeding episodes were WHO grade 2. 
URL http://www.isrctn.com/ISRCTN08758735
 
Title TRIGGER 
Description Feasibility cluster-randomised trial of two different red cell transfusion policies for the management of patients admitted with acute upper intestinal bleeding - a major users of red blood cells supplied by NHSBT. 
Type Therapeutic Intervention - Surgery
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2013
Development Status Under active development/distribution
Clinical Trial? Yes
Impact Awaited 
URL http://www.controlled-trials.com/ISRCTN85757829
 
Description Patient Representative (TSC Membership - HLA Epitope) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Patient Representative is involved as a member of the HLA Epitope TSC. Feedback from Patient Representative on protocol and patient information was used to clarify these documents for future patients.
Year(s) Of Engagement Activity 2013
 
Description Patient group involvement (Membership of TAPS TSC) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Annual Trial Steering Committee (TSC) meetings, regular study updates in the Sickle Cell society's newsletter.


Patient perspectives were included in the design and conduct of the trial.
Patients were made aware of this study and kept updated with the study progress.
The trial results were disseminated in this patient group.
Year(s) Of Engagement Activity Pre-2006,2006,2007,2008,2009,2010,2011