Liverpool School of Tropical Medicine

Bites by venomous snakes can cause disability and can be life-threatening. We are doing research in adult patients to try and find medications that can be administered orally and can help to reduce disability and death due to snakebite. We do not know whether the drugs in this study work in humans and we aim to discover this.
In Stage A, we will provide a new drug or placebo (inactive medication) in community locations, such as rural health clinics, in Brazil and Ghana. Neither the patient nor the clinical team will know which treatment option has been allocated. If a drug were to show signs of working as a treatment during Stage A, it will progress to Stage B. In Stage B, we will provide the drug or antivenom (the current approved treatment for snakebite) in a hospital setting. During Stage B, the patient and the clinician will know which treatment has been received. The purpose of Stage B is to discover whether the drug might hold promise as an alternative treatment to antivenom in the future. Participants will be monitored closely during Stage B and 'rescue antivenom' will be given if they become unwell.
The medications being considered were developed for other health conditions, like cancer, so have been given to patients across the world before. The medications may prove effective at inhibiting the damaging effects of snake venom. Each of the trial drugs could be taken by mouth (oral) in community clinics and ambulances, much sooner than the current treatment for snakebite injuries (antivenom), which is only given within hospitals. They may have other advantages too, like reduced cost and less chance of side effects, including severe allergic reaction. Before a medication is included in the trial it will be reviewed and approved by a group of experts. Before a medication is included in Stage B of the trial it will be reviewed for whether it is safe and effective enough (from Stage A results) to be compared against antivenom.
Stage A Participants will be recruited in the field when they attend a community clinic or ambulance. They will be randomly assigned to receive either a study drug or a placebo. When they arrive at hospital, all participants will receive standard of care antivenom. Participants will continue to take study medication (or matching placebo) for 24 hours, and have frequent blood samples collected during their treatment. Once 20 participants have received the drug and twenty have received the placebo, recruitment for this drug will cease. The difference in the improvement in blood clotting studies (how long it takes to clot) will be compared between the participants receiving the drug and the placebo. If the drug shows an improvement in the clotting studies, then it will proceed to Stage B. If the drug fails to improve the clotting studies, or if it is found to cause unsafe side effects, then it will be rejected from progressing to Stage B.
Stage B Participants will be recruited upon arrival at the hospital site and randomly assigned to receive either a study drug shown to be effective in Stage A or standard-of-care antivenom. Study drugs will be administered for 24 hours, during which all participants will undergo frequent blood sampling. Recruitment for each study drug will stop once 48 participants have received the drug and 48 have received antivenom. The primary comparison will be the improvement in blood clotting parameters between the intervention and control groups. If the study drug is safe and achieves a similar improvement to antivenom - allowing for up to a three-hour delay in effect due to oral absorption compared with intravenous antivenom - it will be considered a promising alternative therapy.
Following a planned 3-day stay in hospital, all participants from Stage A and B will be followed up at 2 and 6 weeks. These follow-up visits can be conducted by telephone, outpatient hospital visit, or home visit, depending on what is most suitable for that individual. The end of study visit will take place at the 6-week visit.

Young people of ages 15-24 years, particularly those in Sub-Saharan Africa, do not optimally take up HIV services (HIV testing, HIV prevention and HIV treatment) and contraception. The number of new HIV infections in this group is disturbingly high and they suffer a lot of illness and death related to HIV. Research has found that four out of five sexually active adolescents in Africa are not using contraception. This means that millions of young people are exposed to unintended pregnancy and the associated negative effects such as unsafe abortions, school drop-out and reduced opportunities for both mother and baby. World Health Organisation have issued new guidelines for a new strategy, self-care, where an individual takes care of their own health and manages their illness with or without the support of a health worker. Self-care has potential to increase the number of young people who use HIV and contraception services. There is not enough information on how self-care can be done in a way that supports people to use services and maintain this use over time. Self-care can be made easier by mobile phone-based digital systems called mHealth, which may work by supporting access of services, for example where products are ordered online, or creating enabling conditions for self-care, for example through facilitating correct information-giving.
With various options for HIV prevention and contraception available, young people may need support/guidance choosing options that suit them. Health workers in overburdened health systems may be too overwhelmed to clearly present all options to guide informed decisions. Decision aids (tools that support patients/users to make informed choices that suit their values and preferences) can enhance self-care by enabling informed decisions. Decision aids for HIV prevention and contraception need to be developed for use in self-care settings. Combining decision aids with mHealth tools can enhance self-care.
This study will be co-developed with students enrolled in colleges/universities in Zimbabwe to develop a self-care strategy that includes mHealth together with decision aids and enables students to optimally use HIV and contraception services.
The study is divided into five stages, and builds on another study where a self-care strategy supported by an mHealth tool (without decision aids) was developed. In the first stage of the current study, preferences for decision aids and attributes to include in the mHealth tool will be obtained using qualitative research and a scoping literature review. In the second stage, findings from the first stage will be used to develop blueprints for two decision aids: one for contraception and the other for HIV prevention. In the third stage, the decision aids will be integrated with the existing mHealth tool through a crowdsourcing activity including students, and experts in health and mHealth. In the fourth stage the self-care strategy supported by mHealth and decision aids will be tested in a pilot at 2 colleges/universities. Finally, the fifth stage be a randomised control trial, across college/universities in Zimbabwe, to see whether the self-care strategy supported by mHealth and decision aids will be effective to promote self-care, and therefore, results in an increase in the uptake of HIV and contraception services. This study will also be applied to make recommendations on how the strategy can be provided outside of college/university contexts.