A multicentre, prospective, open label, randomized comparative clinical trial to evaluate safety and efficacy of Reliance Life Sciences’ Bevacizumab (R-TPR-023) plus standard of care and standard of care alone in COVID 19 Acute Respiratory Distress Syndrome (ARDS) patients with non-invasive ventilation.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 44
- 试验地点
- 7
- 主要终点
- 1. Cumulative Proportion of patients requiring mechanical ventilation (invasive mechanical ventilation or extracorporeal membrane oxygenation) or death by
研究概览
简要总结
Severe Covid-19 infection is associated with hyperactive and dysregulated immune response predominantly marked by inflammatory markers like Ferritin, CRP, IL-6. In addition it is also observed that there is increased activity of Vascular Endothelial Growth Factor (VEGF). As different therapeutic options are tried, even agent that inhibits actions
of VEGF – a monoclonal antibody- Bevacizumab is being tried for this purpose. In a study conducted at China and Italy i.e. Efficacy and tolerability of bevacizumab in patients with severe Covid-19, usage of Bevacizumab was found to have beneficial effects.
This study is planned therefore to evaluate safety and efficacy of Bevacizumab in severe COVID 19 patients.
Bevacizumab of Reliance Life Sciences has undergone non clinical toxicology studies and clinical studies earlier and it has received the marketing authorization for indications like metastatic colorectal carcinoma, non-squamous non-small cell lung cancer etc. It is noted that bevacizumab is tried as off label use in management of Covid-19 ARDS
however data is minimal. In view of above Reliance Life Sciences requests approval for phase II clinical trial in patients of COVID 19 Acute Respiratory Distress Syndrome (ARDS) with noninvasive ventilation.
It is planned to enroll 44 patients and randomly assign them in 1: 1 ratio to receive either RLS Bevacizumab plus standard of care or standard of care alone, so that each group will have 22 patients.
Study will be conducted in ICU Admitted patients, there can be overlap of Screening, Randomization and Dosing with Bevacizumab on the same day. Dosing should occur within 48 hours of ICU admission. Day on which Bevacizumab is administered, is considered as day 0. # Though labelled as visits, the trial participants being ICU admitted patients at enrolment, these may not be actual visits in true sense (unless patient is discharged before 28 days and after discharge visits site for scheduled visits)
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Age: ≥18 – ≤65 years old, male and female patients hospitalized for Covid 19 infection.
- •Recently admitted in ICU (i.e. Enrollment/Randomization should occur within 48 hours of ICU admission).
- •Radiologically confirmed pneumonia.
- •Laboratory confirmed Covid19 infection.
- •Severe COVID 19 pneumonia with ARDS defined as patients with clinical signs of pneumonia plus one of the following: a.
- •respiratory rate >30 breaths/min b.
- •severe respiratory distress or SpO2 <90% on room air.
- •Patients on different modalities of oxygen therapy – High Flow Nasal Cannula Oxygen (>0.4 FiO /30 L/min of oxygen flow) or non-invasive ventilation.
- •Presence of raised inflammatory markers in any one of the following: CRP (CRP> 75 mg/L) or Ferritin (≥ 5 times Upper Limit of Normal) or IL-6 (>40 pg/ml) or D dimer (>1.5 μgFEU/ml).
- •Procalcitonin in normal range (<0.3 μg/L).
- •Women of childbearing potential or men capable of fathering children must agree to use adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, surgical sterilization) during the study and for 6 months after receiving the last administration of study drug.
- •Women of childbearing potential must test negative for pregnancy at screening.
排除标准
- •Unable to obtain informed consent from subject or LAR.
- •Patients with ALT/AST ≥ 5 x upper limit of normal (ULN).
- •Patients with heart disease or clinical symptoms that cannot be well controlled, such as NYHA class II or above of cardiac insufficiency, unstable angina, myocardial infarction within one year, supraventricular or ventricular arrhythmias that need treatment or intervention.
- •Allergic to Bevacizumab and its components.
- •Treatment with immunosuppressive or immunomodulatory therapy (including bevacizumab) within the past 3 months.
- •Platelet count of < 1,00,000 /cmm or absolute neutrophil count (ANC) < 2000/cmm at screening
- •Respiratory failure due to other secondary infections /bacterial sepsis or evidence of multiorgan failure
- •Clinical or laboratory evidence of active tuberculosis or active secondary infections.
- •Subjects who are HIV, HBsAg, HCV test positive.
- •Have participated in other clinical trials in the last 3 months or the investigator is of opinion that it is not in the best interest of patient to get enrolled in the study or any other condition wherein the patient participation would cause concerns about his / her safety.
结局指标
主要结局
1. Cumulative Proportion of patients requiring mechanical ventilation (invasive mechanical ventilation or extracorporeal membrane oxygenation) or death by
时间窗: Day 28
次要结局
- 3. The time to at least a two-category improvement in clinical status relative to baseline on the WHO eight-category ordinal scale.(Day 0 to Day 28 (Any time in between))
- 1. Cumulative Proportion of patients requiring mechanical ventilation (invasive mechanical ventilation or extracorporeal membrane oxygenation) or death by(day14.)
- 9.SOFA (Sequential Organ Failure Assessment) score till patient is in ICU (at baseline(Day 0, day 14 and 28)
- 13. Proportion of patients with non-invasive ventilation(Day 0 to Day 28 (Any time in between))
- 2. The time to hospital discharge or readiness for discharge as assessed with the use of WHO eight-category ordinal scale (with categories ranging from 1 to 8. Higher categories indicating a worse condition)(Day 0 to Day 28 (Any time in between))
- 8. PaO2/FiO2 ratio on admission(Day 2 and Day 7.)
- 10. Days free of supplemental Oxygen(since Day 0)
- 4. The time to clinical failure (the time to death, mechanical ventilation, worsening by two categories from baseline on the eight category ordinal scale], or withdrawal [whichever occurred first]).(Day 0 to Day 28 (Any time in Between))
- 5. All-cause mortality.(Day 0 to Day 28 (Any time in Between))
- 6. Time to PaO2/FiO2 ratio greater than 200.(Day o to Day 28 (Any time In Between))
- 7. Proportion of patients whose clinical status on the World Health Organization 8point ordinal scale is as follows on day 28: Not hospitalized, no limitations on activities.(Day 0 to Day 28 (Any time in Between))
- 14. Duration of non-invasive ventilation(Day 0 to Day 28 (Any time Between))
- 15. Duration of invasive mechanical ventilation(Day 0 to Day 28 (Any time In Between))
- 11. Duration of hospitalization(since Day 0)
- 12. Duration of ICU admission(since Day 0)
- 16. Cumulative incidence of SAEs, Grade 3 and 4 AEs, ADR(Day 0 to Day 28 (Any time In between))