COVIDPhase 3NCT04425915
Efficacy of Convalescent Plasma Therapy in Patients With COVID-19
A Phase 3 study testing Convalescent Plasma in people with COVID, run by Institute of Liver and Biliary Sciences, India at 3 sites in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID
- What is being tested?
- Convalescent Plasma
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 3 sitesIndia
- Study dates
- 14 Jun 2020to 15 Dec 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Recipient Inclusion Criteria:
- 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
Recipient Exclusion Criteria:
- 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
Donor Inclusion Criteria for Plasmapheresis
- 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.
Donors Exclusion Criteria:
- Do not 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 and have not been tested for HLA antibodies or are HLA antibody positive if tested and previously transfused donors (to prevent TRALI)
- Donors who have taken steroids during treatment for COVID-19
Trial locations and contacts
3 sites in 1 country.
India3 sites
Maulana Azad Medical College
New Delhi, National Capital Territory of Delhi, 110006
Institute of Liver & Biliary Sciences
New Delhi, National Capital Territory of Delhi, 110070
Rajiv Gandhi Super Speciality Hospital
New Delhi, National Capital Territory of Delhi, 110093
About this study
Official title: Efficacy of Convalescent Plasma Therapy in Patients With COVID-19: A Randomized Control Trial
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.
Read the detailed description
Study Centres:
Institute of Liver and Biliary Sciences Sector D-1, Vasant Kunj New Delhi -110070
- Collection and testing of Convalescent Plasma
Treatment Centres
Lok Nayak Jai Prakash Hospital (LNJP)
Rajiv Gandhi Super-speciality Hospital (RGSSH)
Methodology Donor Plasmapheresis COVID-19 recovered patients will be counseled and informed regarding convalescent plasma donation. The contact information of those who agree will be sent to the coordinator at ILBS Blood Centre.
- The prospective donor will be contacted and if willing to come for donation, the donor will be provided conveyance if required, to come to ILBS Blood centre for Plasma Donation
- At ILBS the donor will be counseled and the doctor in-charge will explain the procedure to the Donor.
- The donor will be given a Donor Information Sheet and Informed consent will be taken on the document
- The eligibility for plasma donation will be ascertained through Medical History, Physical Examination, and laboratory tests.
Donor Eligibility for Plasmapheresis
- 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.
The following Donors will be excluded
- Do not 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 and have not been tested for HLA antibodies or are HLA antibody positive if tested and previously transfused donors (to prevent TRALI)
- Donors who have taken steroids during treatment for COVID-19 Donor Selection Process
- A detailed medical history of the donor will be taken and documented
- Physical examination ( Height, Weight, Blood Pressure, Temperature, adequate veins for phlebotomy)
- Laboratory Testing: complete Blood count, Testing for hepatitis B virus, hepatitis C virus, HIV, malaria, and syphilis) by serology, blood grouping, and antibody screening. Serum protein will be done in repeat donors ( Ref: D\&C Act and Rules)
- Serum COVID-19 specific IgG antibody positive (with an IgG titre higher than 80).
- All Results Evaluated \& Clinically Correlated The donor is deemed eligible/non-eligible
Plasmapheresis Procedure
- Determine Volume to be collect-approx. 500 ml
- As per the Drugs \& Cosmetics Act 1940 and Rules 1945, amended 11.03.2020
- Start Donor Plasmapheresis Procedure(As per SOP)
- Collect Convalescent Plasma The convalescent plasma will be properly labeled and frozen at -80o C in a separate Deep Freezer. It will not be issued to other patients who are with non-COVID.
- Label Details: As per the Drugs \& Cosmetics Act 1940 and Rules 1945, amended 11.03.2020.
- Storage condition- Below -30oC
- Shelf life: - 1 Year
Other Sources of Convalescent Plasma:
Convalescent Plasma collected during a CP donation drive by Delhi Govt. following all rules and regulations of the Drugs\& Cosmetics Act 1940 and Rules 1945, amended 11.03.2020 is stored at ILBS and will be used in this trial.
The tests for Donors:
- Real-time PCR for SARS-CoV-2: Nasal swab samples will be taken prior to donation and tested for SARS-CoV-2 by real-time PCR method it the donor does not have two negative reports 24 hrs apart.
Antibody Titers of Convalescent Plasma and Patients Plasma by ELISA
For Donors:
The titre of serum neutralizing antibody which is the spike protein antibody, directed against the SARS-CoV-2 RBD (receptor binding domain) proteins. The titre will be done by IgG ELISA or by Rapid IgG antibody titre. The minimum titre of 80 is needed for the use of convalescent in patients.
For recipients:
- Real-time PCR for SARS-CoV-2: Nasal swab samples will be taken prior to transfusion and tested for SARS-CoV-2 by real-time PCR method. The test should be positive for eligibility of the recipient along with clinical criteria for COVID-19.
- Antibody titre: The serum of each recipient will be obtained and IgG antibody titre by enzyme-linked immune-sorbent assay (ELISA) or Rapid IgG antibody method will be tested one day prior to the convalescent plasma transfusion. Changes of IgG antibody titre before and after convalescent plasma transfusion in patients will be studied. The serum will be stored for neutralizing antibody titers by plaque reduction will be done subject to availability.
Study Population:
Adult patients with severe COVID -19 infections defined as WHO Interim Guidance and the Guideline of Diagnosis and Treatment of COVID-19 of National Health Commission of China (version 5.0) 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
Study Design:
An open label randomized controlled trial. The study group will comprise of 400 adult patients with severe COVID -19 as detailed above.
Randomization will be done in the ratio of 1:1 in with 200 patients in the treatment arm and 200 patients in the control arm. Allocation concealment will be done by Sequentially Numbered Opaque Sealed Envelopes (SNOSE) method.
Intervention Arm: 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 Control Arm: Standard of Care will be given to severely sick COVID-19 patients in the control arm Details of Standard of Care 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.) Monitoring and Assessment: Daily until clinical improvement Adverse Effects: Will be documented Stopping rule: None (C) The expected outcome of the project: Investigator expect convalescent plasma therapy to be a safe and efficacious therapy based on our pilot RCT. This study will determine if there is a clinical improvement /mortality benefit and further elaborate on its safety in patients with severe COVID-19
- Conditions
- COVID
- Being tested
- Convalescent Plasma, Standard of Care
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Convalescent PlasmaBiological
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
Standard of CareOther
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.)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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.) Receives: Other: Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- death=6;
- hospital admission for extracorporeal membrane oxygenation or mechanical ventilation=5;
- hospital admission for non-invasive ventilation or high-flow oxygen therapy=4;
- hospital admission for oxygen therapy (but not requiring high-flow or non-invasive ventilation)=3;
- hospital admission but not requiring oxygen therapy=2;
- 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.
Measured: Day 28
Secondary outcomes (18)
Proportion of patients in each category according to the ordinal scale
Measured: 48 hours
Proportion of patients in each category according to the ordinal scale
Measured: 7 day
Proportion of patients in each category according to the ordinal scale
Measured: Day 14
Proportion of patients in each category according to the ordinal scale
Measured: Day 28
Duration of oxygen therapy in both groups
Measured: Day 28
Duration of hospital stay in both groups
Measured: Day 28
Proportion of patients on mechanical ventilation at day 7 in both groups
Measured: Day 7
Mortality in both groups
Measured: Day 7
Mortality in both groups
Measured: Day 28
Duration of Intensive Care Unit stay
Measured: Day 28
Incidence of adverse effects in both groups
Measured: Day 28
Presence of antibodies against SARS-CoV-2 in serum after plasma administration
IgG Titres against S1, RBD antigen, and SARS CoV2 neutralizing antibody titres
Measured: Day 0
Presence of antibodies against SARS-CoV-2 in serum after plasma administration
IgG Titres against S1, RBD antigen, and SARS CoV2 neutralizing antibody titres
Measured: Day 3
Presence of antibodies against SARS-CoV-2 in serum after plasma administration
IgG Titres against S1, RBD antigen, and SARS CoV2 neutralizing antibody titres
Measured: Day 7
Presence of antibodies against SARS-CoV-2 in serum after plasma administration
IgG Titres against S1, RBD antigen, and SARS CoV2 neutralizing antibody titres
Measured: Day 14
Change in Cytokines in both groups
Measured: Day 28
Change in acute phase reactants in both groups
Serum ferritin
Measured: Day 28
Correlation of the titers in COVID-19 convalescent plasma donors with duration of illness, the severity of symptoms, duration of hospital stay, drugs used in therapy, duration between recovery, and donation.
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start14 Jun 2020
- Primary completion15 Dec 2020
- Study completion15 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVIDStudies of the same condition, open and under way.
- More trials run by Institute of Liver and Biliary Sciences, IndiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 400 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Liver and Biliary Sciences, India
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04425915
- Sponsor's protocol ID
- ILBS-COVID-04
- Status last verified
- Jun 2021
- First submitted
- 7 Jun 2020
- Last updated
- 14 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
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.
PubMed 35387813
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Convalescent Plasma Therapy in Patients With COVID-19: A Randomized Control Trial
- ClinicalTrials.gov ID
- NCT04425915
- Acronym / sponsor ID
- ILBS-COVID-04
- Conditions
- COVID
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 400 participants (actual)
- Lead sponsor
- Institute of Liver and Biliary Sciences, IndiaUniversity, hospital or other
- Study start
- 14 Jun 2020 (actual)
- Primary completion
- 15 Dec 2020 (actual)
- Study completion
- 15 Dec 2020 (actual)
- First posted
- 11 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Study Centres:
Institute of Liver and Biliary Sciences Sector D-1, Vasant Kunj New Delhi -110070
- Collection and testing of Convalescent Plasma
Treatment Centres
Lok Nayak Jai Prakash Hospital (LNJP)
Rajiv Gandhi Super-speciality Hospital (RGSSH)
Methodology Donor Plasmapheresis COVID-19 recovered patients will be counseled and informed regarding convalescent plasma donation. The contact information of those who agree will be sent to the coordinator at ILBS Blood Centre.
- The prospective donor will be contacted and if willing to come for donation, the donor will be provided conveyance if required, to come to ILBS Blood centre for Plasma Donation
- At ILBS the donor will be counseled and the doctor in-charge will explain the procedure to the Donor.
- The donor will be given a Donor Information Sheet and Informed consent will be taken on the document
- The eligibility for plasma donation will be ascertained through Medical History, Physical Examination, and laboratory tests.
Donor Eligibility for Plasmapheresis
- 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.
The following Donors will be excluded
- Do not 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 and have not been tested for HLA antibodies or are HLA antibody positive if tested and previously transfused donors (to prevent TRALI)
- Donors who have taken steroids during treatment for COVID-19 Donor Selection Process
- A detailed medical history of the donor will be taken and documented
- Physical examination ( Height, Weight, Blood Pressure, Temperature, adequate veins for phlebotomy)
- Laboratory Testing: complete Blood count, Testing for hepatitis B virus, hepatitis C virus, HIV, malaria, and syphilis) by serology, blood grouping, and antibody screening. Serum protein will be done in repeat donors ( Ref: D\&C Act and Rules)
- Serum COVID-19 specific IgG antibody positive (with an IgG titre higher than 80).
- All Results Evaluated \& Clinically Correlated The donor is deemed eligible/non-eligible
Plasmapheresis Procedure
- Determine Volume to be collect-approx. 500 ml
- As per the Drugs \& Cosmetics Act 1940 and Rules 1945, amended 11.03.2020
- Start Donor Plasmapheresis Procedure(As per SOP)
- Collect Convalescent Plasma The convalescent plasma will be properly labeled and frozen at -80o C in a separate Deep Freezer. It will not be issued to other patients who are with non-COVID.
- Label Details: As per the Drugs \& Cosmetics Act 1940 and Rules 1945, amended 11.03.2020.
- Storage condition- Below -30oC
- Shelf life: - 1 Year
Other Sources of Convalescent Plasma:
Convalescent Plasma collected during a CP donation drive by Delhi Govt. following all rules and regulations of the Drugs\& Cosmetics Act 1940 and Rules 1945, amended 11.03.2020 is stored at ILBS and will be used in this trial.
The tests for Donors:
- Real-time PCR for SARS-CoV-2: Nasal swab samples will be taken prior to donation and tested for SARS-CoV-2 by real-time PCR method it the donor does not have two negative reports 24 hrs apart.
Antibody Titers of Convalescent Plasma and Patients Plasma by ELISA
For Donors:
The titre of serum neutralizing antibody which is the spike protein antibody, directed against the SARS-CoV-2 RBD (receptor binding domain) proteins. The titre will be done by IgG ELISA or by Rapid IgG antibody titre. The minimum titre of 80 is needed for the use of convalescent in patients.
For recipients:
- Real-time PCR for SARS-CoV-2: Nasal swab samples will be taken prior to transfusion and tested for SARS-CoV-2 by real-time PCR method. The test should be positive for eligibility of the recipient along with clinical criteria for COVID-19.
- Antibody titre: The serum of each recipient will be obtained and IgG antibody titre by enzyme-linked immune-sorbent assay (ELISA) or Rapid IgG antibody method will be tested one day prior to the convalescent plasma transfusion. Changes of IgG antibody titre before and after convalescent plasma transfusion in patients will be studied. The serum will be stored for neutralizing antibody titers by plaque reduction will be done subject to availability.
Study Population:
Adult patients with severe COVID -19 infections defined as WHO Interim Guidance and the Guideline of Diagnosis and Treatment of COVID-19 of National Health Commission of China (version 5.0) 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
Study Design:
An open label randomized controlled trial. The study group will comprise of 400 adult patients with severe COVID -19 as detailed above.
Randomization will be done in the ratio of 1:1 in with 200 patients in the treatment arm and 200 patients in the control arm. Allocation concealment will be done by Sequentially Numbered Opaque Sealed Envelopes (SNOSE) method.
Intervention Arm: 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 Control Arm: Standard of Care will be given to severely sick COVID-19 patients in the control arm Details of Standard of Care 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.) Monitoring and Assessment: Daily until clinical improvement Adverse Effects: Will be documented Stopping rule: None (C) The expected outcome of the project: Investigator expect convalescent plasma therapy to be a safe and efficacious therapy based on our pilot RCT. This study will determine if there is a clinical improvement /mortality benefit and further elaborate on its safety in patients with severe COVID-19
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Convalescent Plasma with Standard of Care | Experimental | Biological: Convalescent Plasma, Other: Standard of CareTwo 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 |
| Standard of Care | Active comparator | Other: Standard of CareThe 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.) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Convalescent PlasmaDose-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 | Biological | Convalescent Plasma with Standard of Care |
| Standard of CareThe 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 | Convalescent Plasma with Standard of Care, Standard of Care |
Primary outcome
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)
Time frame: Day 28
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.
18 secondary outcomes
Proportion of patients in each category according to the ordinal scale
Time frame: 48 hours
Proportion of patients in each category according to the ordinal scale
Time frame: 7 day
Proportion of patients in each category according to the ordinal scale
Time frame: Day 14
Proportion of patients in each category according to the ordinal scale
Time frame: Day 28
Duration of oxygen therapy in both groups
Time frame: Day 28
Duration of hospital stay in both groups
Time frame: Day 28
Proportion of patients on mechanical ventilation at day 7 in both groups
Time frame: Day 7
Mortality in both groups
Time frame: Day 7
Mortality in both groups
Time frame: Day 28
Duration of Intensive Care Unit stay
Time frame: Day 28
Incidence of adverse effects in both groups
Time frame: Day 28
Presence of antibodies against SARS-CoV-2 in serum after plasma administration
Time frame: Day 0
Presence of antibodies against SARS-CoV-2 in serum after plasma administration
Time frame: Day 3
Presence of antibodies against SARS-CoV-2 in serum after plasma administration
Time frame: Day 7
Presence of antibodies against SARS-CoV-2 in serum after plasma administration
Time frame: Day 14
Change in Cytokines in both groups
Time frame: Day 28
Change in acute phase reactants in both groups
Time frame: Day 28
Correlation of the titers in COVID-19 convalescent plasma donors with duration of illness, the severity of symptoms, duration of hospital stay, drugs used in therapy, duration between recovery, and donation.
Time frame: Day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2021.
- Derived from this study: PubMed 35387813Bajpai 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.
- Individual participant dataSharing planned: Yes
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Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
Recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19
Post SARS-CoV2 (COVID-19)
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Convalescent Plasma in people with COVID, run by Institute of Liver and Biliary Sciences, India at 3 sites in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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) (time frame: Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04425915, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2021.