Covid-19 Living Data

Trial CTRI/2020/09/027903
Publication Parikh D, Indian Pract (2021) (published paper)

Funding: Private (Intas Pharmaceuticals Ltd., India)
Conflict of interest: Yes

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / India Follow-up duration (days): 28
Inclusion criteria	18 to 65 years laboratory-confirmed SARS-CoV-2 infection as determined by reverse transcription-polymerase chain reaction (RT-PCR) within <72 hours before randomization moderate or severe active COVID-19 (Clinical Management of COVID-19 Guidelines of MOHFW Ver. 05) the female participant having a negative pregnancy test. 1. Participant and/or legally acceptable representative must sign an ICF to participate in the study indicating that the participant understands the purpose of, and procedures required for the study as described in this protocol and is willing to and will be able to adhere to requirement of the protocol 2. Participant must be 18 to 65 years of age (both inclusive), at the time of signing the informed consent 3. Participants must have documented laboratory-confirmed SARS-CoV-2 infection as determined by reverse transcription- polymerase chain reaction (RT-PCR) in any specimen, within <72 hours prior to randomization 4. Participants with moderate or severe active COVID-19 (Clinical Management of COVID-19 Guidelines of MOHFW) at screening and baseline defined as, a. Radiological evidence of pulmonary infiltrates or Clinical features such as dyspnea and/or hypoxia, fever, cough, b. SpO2 of <94 % on room air, and c. Respiratory rate of ≥24 per minute 5. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: a. Is not a woman of childbearing potential (WOCBP), Or Is a WOCBP and using an acceptable contraceptive method as described in Appendix 10.4 of the protocol during the intervention period and at a minimum 30 days until after the last dose of study intervention. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. b. A WOCBP must have a negative highly sensitive pregnancy test (serum) within 4 days before the first dose of study intervention. c. Additional requirements for pregnancy testing during and after study intervention are in Appendix 10.2 of the protocol. d. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy 6. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of study intervention: a. Must agree not to donate sperm for the purpose of reproduction, PLUS b. Must agree to use contraception /barrier as detailed below: i. a male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person. ii. Should also be advised of the benefit for a female partner to use a highly effective method of contraception described in Appendix 10.4 of the protocol as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
Exclusion criteria	More than 5 days of COVID-19 specific hospitalization had symptoms for more than 10 days, required invasive ventilation or having hemodynamic instability (MOHFW guideline) or multiple organ dysfunction/failure or evidence of bacterial super-infection 1. Participant requiring invasive ventilation or having hemodynamic instability (MOHFW guideline) or multiple organ dysfunction/failure or evidence of bacterial superinfection (as defined by Procalcitonin level ≥0.5 µg/L or other applicable diagnostic parameters as per standard medical care) as per the independent clinical judgment of the Investigator at screening and /or baseline 2. Documented medical history of known allergies, hypersensitivity, or intolerance to intravenous immunoglobulin or other injectable form of IgG or blood products 3. Documented medical history of known IgA deficiency 4. Participants with a lifetime history of at least one thrombotic event including deep vein thrombosis, cerebrovascular accident, pulmonary embolism, transient ischemic attacks, or myocardial infarction 5. Participants who have received any blood products within 30 days prior to randomization 6. Participant with more than 5 days of COVID-19 specific hospitalization prior to the first administration of treatment at baseline 7. Participants who have more than 10 days between the onset of symptoms and the day of first administration of treatment at baseline 8. Pregnant or breastfeeding female participants 9. Currently receiving renal replacement therapy/dialysis OR Creatinine clearance < 50 mL/min using the Cockcroft-Gault formula 10. Documented medical history of hepatitis B surface antigen (HbsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HbsAg or anti-HCV at Screening 11. Documented medical history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening 12. Currently receiving or has received in the last 14 days, experimental immune modulators, and/or monoclonal antibody therapies 13. Confirmed diagnosis of bacterial pneumonia or other active/uncontrolled fungal or viral infections at screening/baseline 14. Participants who have received organ transplantation or major surgery in the past 6 months 15. Participants whose ALT/AST levels are 5 times higher than the normal upper limit and total bilirubin is 3 times higher than the upper limit of normal 16. Co-morbid systemic illnesses (uncontrolled diabetes, uncontrolled hypertension, cardiac disease, chronic lung disease, chronic kidney disease, immune-suppression and cancer or other severe concurrent disease) which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed treatment 17. Current participation in another interventional clinical trial (with an investigational drug) that is not an observational registry and have received an investigational intervention 30 days or 5 half-lives (whichever is longer) before the signing the consent 18. Participation in any other clinical trial of an experimental treatment for COVID19 19. Any other clinical/social/ psychiatric condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g. compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments 20. Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site.
Interventions
	Treatment C-IVIG 30 mL IV on day 1 and 2
	Control Standard care
Participants
	Randomized participants : C-IVIG=30 Standard care=30
	Characteristics of participants N= 60 Mean age : NR 44 males Severity : Mild: n=0 / Moderate: n=37 / Severe: n=23 Critical: n=0 Number of vaccinated participants: NR
Primary outcome
	In the register Mean change from Day 1 to Day 8 in clinical outcome of treatment with COVID-19 Hyper-Immuneglobulin (Human) as compared to the control arm as assessed by 8-point ordinal scale
	In the report mean change from day 1 to day 8 in an 8-point ordinal scale
Documents available	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the preprint and published articles, the registry (dated Sept 18, 2020) was used for data extraction and analysis. The study achieved the target sample size specified in the trial registry. There is no change from the trial registration in the intervention and control treatments. The primary outcome indicated in registry reflects the primary outcome reported in the paper however, the preprint also reports on incidence of viral conversion (D7) which was not prespecified. The study was updated on March 17th, 2022 with data extracted from contact with authors. The study was also published in the Indian Practitioner Journal. Data from this is presented.