口服社区蛇毒金属蛋白酶抑制剂治疗蛇咬伤的试验 (TOCSINS)

安慰剂比较：口服安慰剂阶段 A

药品：口服安慰剂胶囊

口服安慰剂

有源比较器：B 阶段 IV 抗蛇毒血清

药品：抗蛇毒血清蛇类

该国推荐的静脉注射抗蛇毒血清标准疗法

实验性的：阶段A和B口服DMPS

药品：2,3-二巯基-1-丙磺酸

口服给药

其他名称：

• 二巯丙醇
• DMPS

实验性的：A期和B期口服马立马司他

药品：马立马司他

口服给药

实验性的：B期IV级马立马司他

药品：马立马司他

口服给药

Mean time until lab INR is less than 50% of the baseline value (efficacy)

Stage A and B - The mean time until the lab INR is <50% of the baseline value (or less than 1.4 if the baseline value is <2.8) on two consecutive measurements per treatment arm. Time is measured starting from randomisation. Time is measured until the first of the two consecutive measurements being <50% or <1.4. Baseline INR sample is defined as blood collected day 0 post-consent and prior to treatment administration.

Incidence (cumulative) of safety events (safety)

Stage A and B- Incidence (cumulative) of any AE, non-serious AE, SAE, SAR, SUSAR. Cumulative incidence is calculated as the number (%) of participants who experience at least one AE in the pre-specified groups.

Stage A- Assess the effect of pre-hospital treatment on INR improvement based on travel time to hospital.

Stage A- Assess the effect of pre-hospital treatment on INR improvement based on travel time to hospital. Amongst participants with baseline INR ≥1.4, the log change in INR, from pre-hospital baseline to hospital arrival, will be analysed using a linear regression model with treatment group, travel time, and their interaction

Stage A- Assess the effect of pre-hospital treatment on fibrinogen improvement based on travel time to hospital.

Stage A- Assess the effect of pre-hospital treatment on fibrinogen improvement based on travel time to hospital. Amongst participants with baseline INR ≥1.4, the log change in fibrinogen from pre-hospital baseline to 12 hours after randomisation, will be analysed using a linear regression model with treatment group, travel time, and their interaction.

Stage A and B- To determine the acceptability of the intervention between treatment arms in terms of quality of life.

Stage A and B- to determine the acceptability of the intervention between treatment arms as a patient-reported outcome of functioning. Assessed using the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0), a 12-item validated scale measuring disability across six life domains (cognition, mobility, self-care, interpersonal interaction, life activities, and participation). Scores range from 0 to 48, where higher scores indicate greater disability.

Unit of Measure: Units on a scale (0-48)

Stage A and B- To determine the acceptability of the intervention between treatment arms as patient-reported outcomes of functioning.

Assessed using the Patient Specific Functional Scale (PSFS), in which participants rate their ability to perform up to three self-nominated activities on a numerical scale from 0 to 10, where 0 indicates inability to perform the activity and 10 indicates full pre-injury ability. Higher scores indicate better function. Unit of Measure: Units on a scale (0-10).

Stage A and B- To evaluate the reach of the intervention (Participant refusal rate)

Stage A and B- To evaluate the reach of the intervention. Monitor enrolment data based on % refusal.

Measurement: Percentage of eligible patients who decline participation Unit of measure: Percentage (%)

Stage A and B- To evaluate the reach of the intervention (Exclusion rate)

Stage A and B- To evaluate the reach of the intervention. Monitor enrolment data based on % exclusion.

Measurement: Percentage of screened patients excluded due to protocol-defined exclusion criteria.

Unit of measure: Percentage (%)

Stage A and B- To evaluate the reach of the intervention (Time between bite and treatment received)

Stage A and B- To evaluate the reach of the intervention. Monitor enrolment data based on time between bite and treatment received.

Measurement: Time elapsed between reported snakebite and receipt of study treatment.

Unit of measure: Hours

Stage A and B-To evaluate the reach of the intervention based on recruitment rate across the study catchment area (Recruitment rate)

Stage A and B- To evaluate the reach of the intervention. Monitor enrolment data based recruitment rate across the study catchment area.

Measurement: Rate of participant enrolment across the study catchment area. Unit of measure: Participants per site per month

Stage A and B- Identify benefits of and barriers for future implementation of the intervention.

Stage A and B- Identify benefits of and barriers for future implementation of the intervention. Mixed-methods following the Consolidated Framework Implementation Research interviewing participants and health care providers

Stage A- To determine differences in resolution of clinically relevant non-serious bleeding events.

Stage A- To determine differences in resolution of clinically relevant non-serious bleeding events. Amongst all participants with non-major bleeding (epistaxis, gingival bleeding, or bleeding from a venepuncture site for >5 min) at randomisation, proportion with cessation of bleeding on arrival to the hospital site per treatment arm.

Stage B- Assess the effect of time to treatment on INR improvement (based on estimated time from bite until administration of the treatment).

Stage B- Assess the effect of time to treatment on INR improvement (based on estimated time from bite until administration of the treatment). Amongst participants with baseline INR ≥1.4, change in INR from baseline to 6 hours, analysed using a linear regression model with treatment group, estimated time from bite to treatment, and their interaction

Stage B- Assess the effect of time to treatment on fibrinogen improvement (based on estimated time from bite until administration of the treatment).

Stage B- Assess the effect of time to treatment on fibrinogen improvement (based on estimated time from bite until administration of the treatment). Amongst participants with baseline INR ≥1.4, change in fibrinogen from baseline to 12 hours, analysed using a linear regression model with treatment group, estimated time from bite to treatment, and their interaction

Stage B- To determine differences in resolution of clinically relevant non-serious bleeding events.

Stage B- To determine differences in resolution of clinically relevant non-serious bleeding events. Amongst all participants with non-major bleeding (epistaxis, gingival bleeding, or bleeding from a venepuncture site for >5 min) at randomisation, proportion with cessation of bleeding at 3 hours after randomisation per treatment arm.