Randomised controlled trial of podoconiosis treatment in northern Ethiopia.

Podoconiosis is one of the forgotten types of leg swelling (elephantiasis) in the tropics. Unlike the other, better-known types of leg swelling, podoconiosis is not caused by any parasite, virus or bacterium, but by an abnormal reaction to minerals found in the clay soils of some tropical highland areas. Although an estimated 4 million people are affected by podoconiosis across Africa, there is no government health service provision for patients in any endemic country. In Ethiopia, where 1 million people with podoconiosis live, non-government organizations (NGOs) have been responsible for the development of simple treatment methods using low-cost, locally accessible materials. Treatment takes the form of foot hygiene, skin care, bandaging, exercises to improve lymph drainage and use of socks and shoes. Although the NGOs consider the treatment to be effective, no formal test has yet been conducted.
Our main objective is to test whether the 'standard' treatment reduces the number of times a patient experiences 'acute episodes', when the leg become hot, painful and more swollen than usual. These episodes significantly compromise patients' ability to work or carry out normal day-to-day tasks. We will also test whether the effectiveness of 'standard' treatment can be increased by first giving daily lymph drainage massage for two weeks. We will measure the cost-effectiveness of both types of treatment in relation to the costs of living with untreated disease.
The trial will be sited in northern Ethiopia, where 3% of the adult population is affected by podoconiosis. Prior to the trial, an economic context survey will be performed to supply background information on typical work hours and settings, labour and medical costs and productivity losses related to podoconiosis. The trial will also be preceded by rapid ethical assessment to identify optimal methods of conveying information about the trial and the approaches to obtaining informed consent preferred by the community.
We have identified and located at least 2000 patients who need treatment but are not yet receiving it. We plan to randomly allocate 900 of these patients to one of three groups: either to 'standard' treatment, or to 'intensive' treatment or to delayed treatment. Provision of care will be organised through the IOCC Podoconiosis Project, which already has excellent links with the community and local government. The randomisation process, data monitoring and statistical analysis will be overseen by experts at the Clinical Trials Facility in Kilifi, Kenya, who will make twice-yearly visits to the trial site. Data collection will be performed monthly by a team of 10 recruited specifically for the task, and independent of the community project assistants providing care. More detailed examination will be performed at 6 months and 1 year. The Clinical Trials Facility will ensure data quality, will monitor safety reports and will supervise data analysis, building capacity within Ethiopia for future clinical trials through frequent training and monitoring visits.
The results of the trial will be disseminated through a workshop in Addis Ababa to government and non-government organizations affiliated to the Ethiopian National Podoconiosis Action Network; through peer-reviewed publications and Footwork (the new International Podoconiosis Initiative) to stakeholders in other podoconiosis-endemic countries.

The objective of this trial is to test the effectiveness of lymphoedema management in podoconiosis patients. We plan to achieve this using a pragmatic, single-blind, randomised controlled trial (RCT) with three intervention 'arms' that will compare two models of podoconiosis lymphoedema management in the community with delayed treatment (as control).

'Standard' podoconiosis lymphoedema intervention consists of twice-weekly group meetings with instruction and practical demonstration of foot hygiene by a community project assistant. Management comprises: foot hygiene, use of emollient, bandaging, exercises to improve lymph drainage, elevation of the foot of the bed and use of shoes and socks. 'Intensive' podoconiosis lymphoedema management consists of 'standard' plus additional 5 times per week clinic-based manual lymphatic drainage for one hour for the first two weeks.

900 adult podoconiosis patients located in independent households will be randomised, 300 to each arm. The primary outcome is incidence of acute dermatoadenolymhangitis (ADLA, a common, debilitating complication of untreated podoconiosis). Secondary outcomes include adherence with treatment, clinical stage of disease, lower leg and foot circumference, quality of life, prevalence of entry lesions, duration of ADLA, perceived stigma and economic productivity. The principal analyses will be conducted at 6 and 12 months of follow-up, and will be based on the rate of ADLA events using multivariable Poisson regression.

Results will be disseminated rapidly through the National Podoconiosis Action Network in Ethiopia, and through Footwork, the International Podoconiosis Initiative, to stakeholders in other podoconiosis-endemic countries, as well as through more conventional academic channels such as peer-reviewed articles. The demand for information from potential podoconiosis care-giving organisations is high, and application of results is likely to be swift.

Who will benefit from this research?
Beneficiaries of our research will include patients, their families and communities; government and non-government health workers who care for patients with podoconiosis; policy makers and governmental health agencies in endemic countries; and the private sector.

How will they benefit?
Patients, their families and communities: Although not usually fatal, podoconiosis reduces the health and wellbeing of about 4 million people globally and constrains economic development in many countries. Patients are highly stigmatised, excluded from social and religious gatherings and marriage, and disabled in their most economically productive years, losing an estimated 45% of working days to the disease. We aim to collect data demonstrating cost-effectiveness of podoconiosis lymphoedema treatment in order to influence government policy to invest scarce resources to relieve suffering and restore productivity among podoconiosis patients. Improved health and wellbeing will lead to economic benefits for patients and their dependents that will benefit the wider community. Within Ethiopia, patients and their families are likely to experience benefits within 5 years of the completion of the trial, since podoconiosis is already included in the National Integrated Management of NTD Strategy.

Public and voluntary sector health workers: the trial results will be used to influence professional practice, benefitting those who treat podoconiosis patients. Until recently, little information on podoconiosis existed in health curricula in endemic countries, and most health professionals were unaware that treatment was possible. In 2011, the PA worked with Open University to develop an in-service training module for Ethiopian Health Extension Workers (http://labspace.open.ac.uk/mod/oucontent/view.php?id=452781), and evidence from the proposed trial will be added to this and to training materials for other government and non-government health professionals in endemic countries. We anticipate the timeline of adaptations of materials to be within one year of completion of the trial.

Transferable professional skills: in addition to academic skills described elsewhere, staff working on the project will develop a range of skills (e.g. in people, project and finance management; leadership; communication and strategy) appropriate to their role in the project which will be transferable to other sectors in future.

Policy makers in endemic countries: The impact of our earlier research is demonstrated by the formal adoption of podoconiosis as a Neglected Tropical Disease (NTD) by WHO and the inclusion of podoconiosis into the Ethiopian Ministry of Health's Integrated Management of NTD Strategy. We will use these channels and Footwork, the International Podoconiosis Initiative, to bring the results of the proposed trial to policy makers in affected tropical countries. As the host country of the first RCT in podoconiosis, Ethiopia's place as a leader in podoconiosis control will be consolidated, which will have beneficial impact on researchers' careers, and potentially, national pride.

Global funding bodies: The trial results will also be important for those prioritizing decisions at major global funding bodies. Clear evidence of treatment effectiveness will be essential to attract substantial funds towards a global podoconiosis control programme.

Private Sector: Should the lymphoedema treatment trialled prove successful, business opportunities to manufacture the consumables required for treatment will open up. Some of these opportunities will be within government-controlled industries (pharmaceuticals), but others will be open to private investment and entrepreneurship (socks, shoes). The estimated 1 million patients within Ethiopia will create a substantial internal market through both government and private procurement.