Clinical Research Directory

Trial of Oral Community SVMP INhibitors for Snakebite

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.

Analysis of the Efficacy of Pressure Pad vs Pressure Bandage Immobilisation for Snake Bite First Aid in Healthy Volunteers.

Snake bite affects thousands of Australians every year, but few die as a result due to high quality first aid and timely medical care. Good first aid should be simple, standardised, use minimal or readily available equipment, and be able to be utilised effectively with no or minimal training by the rescuer. Over time the first aid methods used to manage snake bite in Australia have been questioned due to issues with efficacy, and some emerging evidence of harm from their use. There is little experimental data in the literature to support current first aid practices, and what exists suggests further research is required. This study aims to examine and compare the effectiveness of two first aid methods by tracking the movement of a mock venom through the body when each first aid method is used. This will provide important information about the suitability of current techniques used in Australia and whether a proposed simpler alternative technique is as effective. Currently, initial treatment of snake bite involves early first aid with the application of a pressure bandage and immobilisation (PBI) of the limb. There is limited data to support the basis of this technique and emerging evidence of harm when applied incorrectly. This project sets out to evaluate PBI compared to another technique involving the application of a pressure pad (PP) at the bite site (which is easier to do, and used in many countries outside of Australia). The project aims to determine whether each technique is effective, and whether the PP technique is at least as effective as PBI. To do this 24 participants will be recruited to undergo study with mock venom injected into their hand or foot and having either PBI or PP applied. The mock venom will then be traced with a gamma camera to determine rate of flow through the lymphatic system, which is how venom travels in the body. It is expected that the project will demonstrate the efficacy of both techniques, and that the PP will be at least as effective as PBI. This will provide a basis for change in the current first aid recommendations for snake bite first aid in Australia, and improve the care provided.

Mapping Snakebite Risk in Ghana and Rwanda

Snakebite causes approximately 138,000 deaths each year and non-fatal bites lead to considerable health burden, particularly in low-income tropical countries. Data on snakebite burden are lacking. Official data from health facilities are often either unavailable or underestimate cases, by excluding the many victims who do not attend formal health facilities; community surveys are useful for assessing burden, but they require significant resources to conduct. This study aims to understand both whether spatial analysis methods can help in assessing and predicting snakebite risk in different environments, and the value of current data collection methods for their contribution to this analysis approach. First, snakebite data already recorded in health facilities in Ghana and Rwanda will be extracted and analysed. Community surveys will be conducted in environmentally diverse areas of Ghana and Rwanda to collect information directly from randomly selected households about their experiences with snakebites. Using GPS to map household locations, geostatistical methods will be applied to the data to see if it can accurately predict areas at high risk of snakebite; the predictions will be used to generate risk maps. The study findings will build knowledge on geographical variation in snakebite risk and help develop an approach to mapping snakebite risk in sub-Saharan Africa. The risk maps generated will be compared with data on the distribution of antivenoms in each country. This will show if antivenoms are available in the places that need them most and help ensure antivenom supplies are better allocated in the future. It will also help identify high-risk areas so health officials can advocate for resources and develop treatment and prevention programmes.