CTRI/2023/10/058782已完成2 期
Randomized, Double-Blinded, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of Intravenous Varespladib Followed by Oral Varespladib in Addition to Standard of Care in Subjects Bitten by Venomous Snakes.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 140
- 试验地点
- 8
- 主要终点
- For subjects bitten by elapids: Time to complete head-lift recovery defined by a 5-second head-lift of 5 second. For subjects bitten by vipers: Area Under the Curve (AUC) of an abbreviated Snakebite Severity Score (SSS) composed of local wound, hematologic, and neurologic subscores from Baseline (pre-dosing) to Day 14
研究概览
简要总结
This is a multicenter,randomized,double-blind, placebo-controlled, phase 2 study designed to evaluate the safety, tolerability and efficacy of a continuous rate infusion (CRI) of IV varespladib followed by transition to the oral dosage form, varespladib-methyl, concurrently with SOC, in participants bitten by venomous snakes.
Approximately 140 male and female eligible participants will be enrolled and randomized to receive active varespladib or placebo (in addition to SOC).
Randomization Ratio 1:1. The randomization will be stratified by snake type: copperhead, Mojave rattlesnake, non-Mojave rattlesnake, Russell’s viper, Elapid, or other, and by age group:140 male and female subjects equally into 2 groups with 10% withdrawal or loss to follow-up anticipated through the time of the assessment of the primary outcome.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 5.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Is a male or female greater than or equal to 5 years of age.
- •Patients must have known or suspected venomous snakebite.
- •In India, enrollment will be restricted to patients bitten by suspected or confirmed Russell’s viper (Daboia russelii) or krait (Bungarus spp.).
- •In the U.S., any snakebite that meets all other criteria may be eligible.
- •Patients must meet one of two categories of inclusion criteria: Category 1: The patient is enrolled within 5 hours of venomous snakebite or symptom onset with an SSS inclusion score of greater than or equal to 2 in one system and greater than or equal to 1 in another system i.e 2+1 OR Category 2: The patient has a suspected or confirmed bite from an elapid and is enrolled within 10 hours of bite or symptom onset with moderate to severe cranial nerve or skeletal muscle weakness.
- •Is willing (or legally authorized representative is willing) to provide informed consent prior to initiation of any study procedures.
- •local wound, pulmonary, cardiovascular, hematologic, or nervous system scores qualify for SSS inclusion criteria.
- •Hematologic score may be used if available, but inclusion should not wait for laboratory results.
- •Point of care tests (e.g., 20WBCT) may be used for enrollment, if used per site standard of care (see Appendix A).
- •GI and Renal scores are not used for inclusion.
- •Isolated ptosis does not meet the definition of moderate to severe neurotoxicity for enrolment.
排除标准
- •Has history of or is suspected to have cerebrovascular accident or intracranial bleeding of any kind, acute coronary syndrome, myocardial infarction, or severe pulmonary hypertension.
- •Has known history of inherited bleeding or coagulation disorder.
- •Is, at Screening Visit, using the following anticoagulants: warfarin/coumadin, argatroban, bilvalirudin, lepirudin, apixaban, dabigatran, clopidogrel, prasugrel, ticlodipine or another anticoagulant agent not specifically listed, or has used heparin, enoxaparin, fondaparinux, or other low molecular weight heparin or any antiarrhythmic drugs within 14 days prior to treatment.
- •Has a history of chronic liver disease such as chronic active viral hepatitis, alcohol-related liver disease, non-alcoholic steatohepatitis, non-alcoholic fatty liver disease, hemochromatosis, primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis.
- •Reports or has known pre-existing renal impairment or chronic kidney disease.
- •Has a known allergy or significant adverse reaction to varespladib or varespladib-methyl.
- •Is considered by the Investigator to be unable to comply with protocol requirements due to geographic considerations, psychiatric disorders, or other compliance concerns.
- •Is pregnant, has a positive urine or serum human chorionic gonadotropin (hCG) pregnancy test or not willing to use a highly effective method of contraception for 14 days after initial treatment, or is breastfeeding.
结局指标
主要结局
For subjects bitten by elapids: Time to complete head-lift recovery defined by a 5-second head-lift of 5 second. For subjects bitten by vipers: Area Under the Curve (AUC) of an abbreviated Snakebite Severity Score (SSS) composed of local wound, hematologic, and neurologic subscores from Baseline (pre-dosing) to Day 14
时间窗: The independent p-values from subjects bitten by elapids and subjects bitten by vipers will be analyzed using Fisher’s combined probability test to obtain a single global p-value for testing the primary endpoint.
次要结局
- Patient Specific Functional Scale (PSFS)(score at Day 3 & Day 7.)
- Complete snakebite severity score (SSS) recovery, defined as a composite score of 0 for the pulmonary cardiovascular local wound hematologic renal & nervous system sections of the SSS at Day 28.(Day 28)
- Total antivenom requirement from Baseline through Day 28(Day 28)
- Duration of hospitalization from Baseline through Day 28(Day 28)
- Change in the composite outcome of the 6-item SSS (pulmonary cardiovascular local wound hematologic renal & nervous system subscores) from Baseline through Day 28(Baseline through Day 28)
- Area under the curve of the composite outcome of the pulmonary, cardiovascular, local wound, hematologic, renal, & nervous system sections of the snakebite severity score (SSS) from Baseline (pre-dosing) to Day 7 for all patients & for patients randomized in Less than equal 5 hours from bite.(Baseline (pre-dosing) to Day 7 for all patients & for patients randomized in Less than equal 5 hours from bite.)
- Change in the 6-item SSS from Baseline through Day 28 using compressed SSS scale(Baseline through Day 28)
- Individual SSS subscores from Baseline through Day 28(Baseline through Day 28)
- Focused hematologic score based on INR & platelets from Baseline through Day 28(Baseline to Day 28)
- Coagulation abnormalities (separately PT, PTT, platelets, & fibrinogen) from Baseline through Day 28(Baseline through Day 28)
- Change in NPRS from Baseline through Day 28(Baseline through Day 28)
- Patient Global Impression of Change (PGIC) from Baseline through Day 28(Baseline through Day 28)
- Clinical Global Impression-Improvement (CGI-I) from Baseline through Day 28(Baseline through Day 28)
- Levels of the myonecrosis marker, creatine kinase (CK), from Baseline through Day 3(Baseline through Day 3)
- For patients bitten by elapids, grip strength from Baseline through Day 28(Baseline through Day 28)
- Elapsed time from initiation of IV varespladib treatment until the transition to oral varespladib-methyl(• All cause mortality through Day 28)
- Patient-Specific Functional Scale (PSFS) average score from Baseline through Day 28(Baseline through Day 28)
- For patients bitten by elapids, change in 5-second head-lift duration from Baseline through Day 28(Baseline through Day 28)
- For patients bitten by elapids, duration of ventilatory support from Baseline through Day 28(Baseline through Day 28)
- Analgesic use from Baseline through Day 28(Baseline through Day 28)
- Transfusion requirement from Baseline (Day 1) through Day 28(Baseline (Day 1) through Day 28)
- Secretory phospholipase A2 (sPLA2) from Baseline through Day 7(Baseline through Day 7)
研究者
研究点 (8)
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