Efficacy of Convalescent Plasma Therapy in Patients With COVID-19

NCT04425915 | Completed Phase 3 DMC

• 1 other identifier: ILBS-COVID-04
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 3

Brief Summary

Currently, no effective treatments are available for the COVID-19. Scientists and Researchers are working on many aspects of treatment options for the development of vaccination and medication to combat this life-threatening problem. Convalescent plasma from recovered COVID-19 patients contains antibodies against COVID-19 which may be beneficial to severely sick COVID-19 patients. Investigator have recently concluded a pilot phase II open-label RCT on the efficacy of convalescent plasma in severe COVID 19 patients in which encouraging results were seen. Investigator plan to further study the efficacy and safety of convalescent plasma in COVID-19 severely sick patients through an RCT. Investigator will collect up to 500 ml Convalescent Plasma from the COVID-19 recovered persons after 14 days of clinical recovery with two consecutive SARS CoV-2 negative tests by PCR at least 24 hours apart. This plasma will be tested and frozen and stored. On requisition it will be thawed and sent to the treating center. Two doses of 250 ml convalescent plasma each will be transfused on two consecutive days to patients who fit the eligibility criteria (Severely sick COVID-19 patients) and are randomized to the convalescent plasma group along with the standard of care and the other group will receive standard of care alone. Data will be collected to study the benefits and adverse events related to convalescent plasma transfusion.

Conditions

COVID

Outcome Measures

Primary Outcomes (1)

• Efficacy of convalescent plasma in severe COVID 19 patients in time to clinical improvement (Clinical improvement: Reduction of two points in ordinal scale or live discharge from the intensive care unit, whichever is earlier)

  The six-point scale is as follows: 1. death=6; 2. hospital admission for extracorporeal membrane oxygenation or mechanical ventilation=5; 3. hospital admission for non-invasive ventilation or high-flow oxygen therapy=4; 4. hospital admission for oxygen therapy (but not requiring high-flow or non-invasive ventilation)=3; 5. hospital admission but not requiring oxygen therapy=2; 6. discharged or having reached discharge criteria (defined as clinical recovery-ie, normalization of pyrexia, respiratory rate 94% on room air, and relief of cough, all maintained for at least 72 h)=1.

  Day 28

Secondary Outcomes (18)

• Proportion of patients in each category according to the ordinal scale

  48 hours

• Proportion of patients in each category according to the ordinal scale

  7 day

• Proportion of patients in each category according to the ordinal scale

  Day 14

• Proportion of patients in each category according to the ordinal scale

  Day 28

• Duration of oxygen therapy in both groups

  Day 28

Study Arms (2)

Convalescent Plasma with Standard of Care

EXPERIMENTAL

Two doses of 250 ml Convalescent plasma from recovered COVID-19 patients + Standard of Care will be given to severely sick COVID-19 patients in the treatment arm

Biological: Convalescent Plasma; Other: Standard of Care

Standard of Care

ACTIVE COMPARATOR

The Ministry of Health and Family Welfare has issued detailed guidelines for the management of sCOVID-19 based on varying grades of severity which may be periodically updated. For the management of ARDS or sepsis the respective guidelines issued by ARDSNet and Surviving Sepsis campaign will be followed. Other institutional protocols for supportive management will be implemented. (Ref: Guidelines on Clinical Management of COVID-19. MoHFW, GoI.2020.)

Other: Standard of Care

Interventions

Convalescent Plasma BIOLOGICAL

Dose-250 ml Frequency - 2 doses on consecutive days Duration -Start by day 3 of symptom onset (of severe COVID-19 as in inclusion criteria) in eligible patients

Convalescent Plasma with Standard of Care

Standard of Care OTHER

The Ministry of Health and Family Welfare has issued detailed guidelines for the management of sCOVID-19 based on varying grades of severity which may be periodically updated. For the management of ARDS or sepsis the respective guidelines issued by ARDSNet and Surviving Sepsis campaign will be followed. Other institutional protocols for supportive management will be implemented. (Ref: Guidelines on Clinical Management of COVID-19. MoHFW, GoI.2020.)

Convalescent Plasma with Standard of Care; Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Patients with severe COVID-19 will be considered for randomization and will be transfused convalescent plasma within 3 days of symptom onset (Severe COVID-19) Severe COVID -19 defined by WHO Interim Guidance and the Guideline of Diagnosis and Treatment of COVID-19 of National Health Commission of China (version 5.0) along with confirmation by real-time RT-PCR assay with severe disease i.e. meeting any 2 of the following criteria-
• Patients on ventilator (in last 24 hours)
• Respiratory distress, RR ≥30 beats/min
• Oxygen saturation level less than 90 % in resting state
• Partial pressure of oxygen (PaO2)/oxygen concentration (FiO2) ≤ 300 mmHg
• Lung infiltrates \> 50% within 24 to 48 hours

You may not qualify if:

• Patient/ family members who do not give consent to participate in the study.
• Patients with age less than 18 years
• Patients presenting with multi-organ failure
• Pregnancy
• Individuals with HIV and Viral Hepatitis and Cancer
• Extremely moribund patients with an expected life expectancy of less than 24 hours
• Hemodynamic instability requiring vasopressors
• Previous history of allergy to plasma
• Cirrhosis
• Severe renal impairment with GFR\< 30ml/min or recipients of RRT, peritoneal dialysis
• Patients with uncontrolled diabetes mellitus, hypertension, arrhythmias and unstable Angina
• Virologically documented (PCR positive by nasopharyngeal swab) who is recovered and free of symptoms for 14 days.
• Has tested negative for SARS CoV 2 on two consecutive tests 24 hrs apart.
• Fulfill all criteria of donor eligibility for donor Plasmapheresis under the Drugs \& Cosmetics Act 1940 and Rules 1945, amended 11.03.2020
• Females who have been pregnant may be tested for anti-HLA antibodies and eligible if negative for the same.

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (3)

Maulana Azad Medical College

New Delhi, National Capital Territory of Delhi, 110006, India

Location

Institute of Liver & Biliary Sciences

New Delhi, National Capital Territory of Delhi, 110070, India

Location

Rajiv Gandhi Super Speciality Hospital

New Delhi, National Capital Territory of Delhi, 110093, India

Location

Related Publications (1)

• Bajpai M, Maheshwari A, Dogra V, Kumar S, Gupta E, Kale P, Saluja V, Thomas SS, Trehanpati N, Bihari C, Agarwal R, Bharti P, Shankar P, Hussain J, Chhabra K, Gupta A, Narayanan A, Agarwal S, Jain S, Bhardwaj A, Kumar G, Yadav BK, Sarin SK. Efficacy of convalescent plasma therapy in the patient with COVID-19: a randomised control trial (COPLA-II trial). BMJ Open. 2022 Apr 6;12(4):e055189. doi: 10.1136/bmjopen-2021-055189.

  PMID: 35387813 DERIVED

MeSH Terms

Interventions

Standard of Care

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2020
• First Posted: June 11, 2020
• Study Start: June 14, 2020
• Primary Completion: December 15, 2020
• Study Completion: December 15, 2020
• Last Updated: October 14, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: After publication till 5 years
• Access Criteria: It will be available for researcher scientist \& government agencies.

Locations

IN (3)