| CTRI Number |
CTRI/2020/05/025346 [Registered on: 25/05/2020] Trial Registered Prospectively |
| Last Modified On: |
25/05/2020 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Biological |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
A Clinical Trial to Assess the Safety and Efficacy of Convalescent Plasma in Severe Covid-19 patients. |
|
Scientific Title of Study
|
A Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma in Severe Covid-19 patients. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| Form CT-06, No. CT/BP/07/2020 |
DCGI |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Latha B |
| Designation |
Associate Professor |
| Affiliation |
Rajiv Gandhi Government General Hospital, Madras Medical College, |
| Address |
Department of Transfusion Medicine, Rajiv Gandhi Government General Hospital, Madras Medical College, Chennai
AJ 45, 9th main road, shanthi colony, Annanagar, Chennai-40
Chennai
TAMIL NADU
600003
India |
| Phone |
9840313152 |
| Fax |
|
| Email |
latsbalu@yahoo.co.uk |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr S Anbuselvi Mattuvar Kuzhali |
| Designation |
Assistant Professor of physiology |
| Affiliation |
Madras Medical College, |
| Address |
Institute of Physiology and Experimental Medicine,
Madras Medical College, Chennai
4B, third floor, KGEYES HYACINTH, LB road, Kamaraj Nagar, Thiruvanmiyur, Chennai
Chennai
TAMIL NADU
600003
India |
| Phone |
9940840760 |
| Fax |
|
| Email |
dranbuselvimk@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
DrJAYANTHI RANGARAJAN |
| Designation |
DEAN |
| Affiliation |
Rajiv Gandhi Government General Hospital, Madras Medical College, |
| Address |
Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai
6A Sagath Srinivas
2nd Street Srinivasapuram
Thiruvanmiyur 600041
Chennai
Chennai
TAMIL NADU
600003
India |
| Phone |
9840025339 |
| Fax |
|
| Email |
rjayanthi363@gmail.com |
|
|
Source of Monetary or Material Support
|
| Secretariat,
Government of Tamilnadu,
Namakkal Kavignar Maaligai,
Fort St. George,Chennai 600 009 |
|
|
Primary Sponsor
|
| Name |
Government of TamilNadu |
| Address |
Health and Family Welfare
Secretariat
Chennai 600009 |
| Type of Sponsor |
Government medical college |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr S Subash |
Rajiv Gandhi Government General Hospital Madras Medical College |
Room.No.204
Tower Block 2, ground floor,
Department of Transfusion Medicine
&
Covid acute care facility
Rajiv Gandhi Government General Hospital
Madras Medical College Chennai
Chennai
TAMIL NADU |
9381715141
dchsub@yahoo.co.in |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional ethics committee, Madras Medical College |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: B972||Coronavirus as the cause of diseases classified elsewhere, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Control Arm |
In control arm are 30 participants who are severe Covid patients being treated in acute care facility and who will be receiving only the standardized acute care treatment for the disease |
| Intervention |
Treatment Arm |
In treatment arm are 30 participants who are severe Covid patients being treated in acute care facility, apart from receiving standardized acute care treatment, they will also be transfused, initially with one unit of 200ml of ABO compatible convalescent plasma and subsequent dose of 200ml after 24 hours of the initial dose. |
|
|
Inclusion Criteria
|
| Age From |
20.00 Year(s) |
| Age To |
50.00 Year(s) |
| Gender |
Both |
| Details |
A. INCLUSION CRITERIA FOR DONOR:
Convalescent plasma: Eligibility of Donor
Potential donors will include the following:
1. Prior diagnosis of COVID-19 documented by a laboratory test , treated and completely recovered from Covid infection.
2. Complete resolution of symptoms and at least one negative lab test for Covid-19 at least 28 days prior to donation (as per NBTC guidelines after Covid -19 pandemic for donor selection).
3. If plasma is collected prior to 28 days after full recovery from illness, then confirmation of the resolution of the infection should be obtained through demonstration of two nasopharyngeal swab tests for SARS-CoV-2 performed at an interval of at least 24 hours on nasopharyngeal swabs.
These individuals will be contacted telephonically and explained the details of the study and their extent of participation. If requested, they will be provided transport for the same.
Donor eligibility criteria:
The following eligibility criteria will be applied towards potential donors:
1. Only males and nulliparous female donors of weight > 55 kgs will be included.
2. Donor eligibility criteria for whole blood donation as per the departmental SOP will be followed in accordance to the Drugs & Cosmetics Act 1940 and rules 1945 therein (as amended till March 2020). Donor will be screened, followed by brief physical examination.
3. Donors not fit to donate blood based on the history and examination will be deferred and excluded from plasma donor pool for a time period specified by country regulation & departmental SOPs.
4. In addition to the afore mentioned donor eligibility criteria, two EDTA samples (5 ml each) and one plain sample (5 ml) will be drawn for the following pre-donation tests as required for convalescent plasmapheresis (CPP).
a) Blood group and antibody screening – Antibody screen positive donors will be deferred.
b) Donors with Hb>12.5g/dl, platelet count>1,50,000 per microliter of blood and TLC within normal limits will be accepted.
c) Screening for HIV, HBV and HCV by serology or NAT. Donor negative by both the tests will be included.
d) Screening for syphilis and malaria by serology. Negative donors will be included
e) Total serum protein. Donors with total serum protein > 6gm/dl will be accepted (as per Drugs and Cosmetics (Second Amendment) Rules, 2020)
f) Presence of IgG and IgM antibodies to covid-19 by quantification test as per manufacturer’s instruction. Donors negative for these will be deferred.
g) Titration of anti-covid-19 (both IgG and IgM) antibodies and SARS-CoV-2 neutralizing antibodies may be done depending on availability of facilities at the time of testing. (Desired titers for IgG antibodies >1024 or neutralizing antibodies >40) doubling dilution of donor serum will be done and titration will be done using CLIA. If not done at the time of plasma collection the donor samples will be stored in aliquots at -80° C to be tested at a later date.
h) Molecular test for covid-19 either from nasopharyngeal swab specimens may be done depending on availability of tests. Donor’s positive will be deferred.
B. INCLUSION CRITERIA FOR RECIPIENT OF CCP:
1. Age should be above 20 years for both genders.
2. Covid positive patients who are under treatment in the covid acute care facility, amongst whom are willing to give consent to participate in this study.
3. Should be admitted in the acute care facility for the treatment of Covid-19 infection without complications.
4. Clinical symptoms suggestive of Covid infection along with confirmed laboratory diagnosis of infection with covid-19 as per ICMR/FDA guidelines.
5. Patients should be classified under severe covid-19 infection without complications criteria as judged by the qualified treating physician.
Criteria for Severe covid-19 are either one or more of the following:
1. Dyspnea should be present.
2. Respiratory rate ≥ 30/min
3. Oxygen saturation ≤ 93%
4. partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300
5. lung infiltrates > 50% within 24 to 48 hours. |
|
| ExclusionCriteria |
| Details |
EXCLUSION CRITERIA FOR DONOR:
Covid-19 infected patients who are under treatment with the criteria:
1. Consecutive 2 swabs positive for covid-19
2. One molecular test for covid-19 positive – RT-PCR.
3. Clinically symptoms suggestive of covid-19.
4. Multiparous female and patient with co morbid conditions.
EXCLUSION CRITERIA FOR RECIPIENTS:
1. Patients with any past history of transfusion reactions to blood products.
2. Receipt of Pooled Immunoglobulin in last 30 days
3. Critically ill patients: respiratory failure, Sepsis, Multiorgan failure, Shock (Requiring Vasopressor to maintain a MAP ≥ 65mmHg or MAP below 65 mmHg)
4. Participating in any other clinical trial
5. Pregnant and lactating women.
6. Patients infected with Covid-19 not under criteria for severe covid condition.
7. Patients with any chronic history of coronary artery disease, coronary bypass surgery, acute pulmonary edema, Pulmonary embolism, Congestive heart failure, Malignant hypertension, Polycythemia Vera, Severe renal failure, Cirrhosis and with any implants. |
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
To prevent progression to severe ARDS (P/F ratio 100) and all-cause Mortality at 1 month.
|
Improvement of clinical symptoms and investigations will be monitored daily for first 3 days, and on day 7, 14, 21, 28, once a month till 3 months. |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Monitoring safety and efficacy pre & post-CCP transfusion:
- Duration(Days) of ICU stay/Hospital stay from symptom onset,
- Duration of mechanical ventilation(Invasive/Non-invasive).
- Incidence of transfusion reactions, ARDS & sepsis,
- Duration of clinical symptoms and Radiological improvement post transfusion
- In-hospital mortality,
- Levels of IgG antibody,neutralizing antibody titers. |
After the CCP transfusion, Serious adverse events will be noted on day 0, 3, 7, 14, 21, 28 and once a month upto 3 months. |
|
|
Target Sample Size
|
Total Sample Size="90"
Sample Size from India="90"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
01/06/2020 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="11"
Days="30" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
not yet. |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
SUMMARY OF STUDY DESCRIPTION: This study trial will provide access to convalescent plasma for patients infected with Covid-19 who are classified by a qualified physician as severe disease and also to assess the safety and efficacy of the therapy. After getting informed written consent, Patient information sheet and recruitment based on the eligibility protocol for donor / recipient, (i) CCP will be collected from donor as per the protocol and (ii) The participants (n=60) are severely ill Covid patients without complications being treated in acute care facility. They will be categorized into 2 (arms) groups –a.) control group [n=30] in which Covid patients who will be receiving only the standardized acute care treatment for the disease andb.) study group (n=30) in which Covid patients apart from receiving standardized acute care treatment, who will also be transfused with one unit of 200ml of ABO compatible convalescent plasma and subsequent dose of 200ml after 24 hours of initial dose – which (CCP) will be obtained from the donor who has recovered from documented infection with Covid-19. Assessment information collected will include the clinical characteristics of the patient plus if any serious adverse events confirmed to be related to the administration of covid convalescent plasma (CCP) from the day of first dose administration with periodical follow-up till 3 months. Other information to be collected retrospectively and for follow up will include: (i) Donor: sociodemographic details, clinical characteristics of the recovered patients, Covid test results with antibody titers, investigations and treatment. (ii) Recipient: Sociodemographic details, Covid facility resource utilization: Clinical characteristics of the patients receiving CCP transfusion such as Days of hospital stay and Days in ICU from symptom onset, Days of mechanical ventilation (invasive/non-invasive), Primary symptoms, associated Comorbidity, In-hospital mortality, treatment of drugs with all investigations included from the day of admission to the hospital and survival to discharge from the acute care facility. Effects of CCP transfusion: Duration of clinical symptoms and Radiological improvement post transfusion, Amelioration of routine laboratory tests for covid disease. Increase in IgG and neutralizing antibody titers and disappearance of Covid-19 RNA. Transfusion reactions/SAE to Covid Convalescent Plasma from the onset of CCP therapy with periodic follow up for 3months. |