January 27th -RCT on REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19

[1/27, 9:30 PM] Biswas Sir Hod: Please share the current RCT on it's efficacy

[1/27, 9:55 PM] Chanku: https://www.nejm.org/doi/full/10.1056/NEJMoa2108163

[1/27, 9:56 PM] Chanku: P-Eligible patients in cohort 1 were 18 years of age or older and were not hospitalized. These patients had a confirmed local SARS-CoV-2–positive diagnostic test result no more than 72 hours before randomization, with the onset of any Covid-19 symptom, as determined by the investigator, occurring no more than 7 days before randomization. Randomization into the initial phase 3 portion of the trial was stratified according to country and the presence of risk factors for severe Covid-19. In the amended phase 3 portion of the trial, only patients with at least one risk factor for severe Covid-19 were eligible. The full list of inclusion and exclusion criteria is provided in the protocol, available at NEJM.org.

All the patients were assessed at baseline for anti–SARS-CoV-2 antibodies — anti-spike (S1) IgA, anti-spike (S1) IgG, and anti-nucleocapsid IgG — and were categorized for the analyses as serum antibody–negative (if all available test results were negative), serum antibody–positive (if any available test result was positive), or other (inconclusive or unknown results).

[1/27, 9:57 PM] Chanku: I-At baseline (day 1), REGEN-COV (diluted in normal saline solution) or saline placebo was administered intravenously. The solutions were indistinguishable and were prepared by qualified personnel who were not associated with the conduct of the trial. Hospitalizations were assessed to be related to Covid-19 by the investigator. The 23-item Symptoms Evolution of COVID-19 instrument, an electronic diary, was used to assess Covid-19 symptoms daily.17 Quantitative virologic analysis of nasopharyngeal swab samples and serum antibody testing, as previously described, were conducted in a central laboratory.16

[1/27, 10:01 PM] Biswas Sir Hod: And O?

[1/27, 10:07 PM] Biswas Sir Hod: The symptom resolution is not significant. 

Unless we know what were the actual events leading to death in the placebo and regencov group, it may not be conclusive efficacy

[1/27, 10:07 PM] Biswas Sir Hod: What risk factor did your patient have?

[1/27, 10:11 PM] Chanku: Primary outcomes were mortality associated with hospitalisation and not to the symptoms themselves sir, 

It just reduces the risk of hospitalization

[1/27, 10:13 PM] Chanku: The median time to resolution of symptoms was 4 days shorter with each REGEN-COV dose than with placebo (10 days vs. 14 days; P<0.001 for both comparisons). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody–positive at baseline. Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was −0.71 log10 copies per milliliter (95% confidence interval [CI], −0.90 to −0.53) in the 1200-mg group and −0.86 log10 copies per milliliter (95% CI, −1.00 to −0.72) in the 2400-mg group. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%); infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups.

[1/27, 10:15 PM] Chanku: She had a good amount of abdominal fat and age was around 50 years sir

[1/27, 10:15 PM] Biswas Sir Hod: No. 

It says hospitalization OR death. 

However how can one combine both these disparate outcomes?

[1/27, 10:15 PM] Biswas Sir Hod: Is that a defined risk factor?

[1/27, 10:16 PM] Chanku: Yes sir, all outpatients who required either hospatalisation and died

[1/27, 10:16 PM] Biswas Sir Hod: This is not significant. 

More serious reactions with placebo? Are they serious?

[1/27, 10:16 PM] Chanku: These factors the study has considered while including patients also diabetes

[1/27, 10:17 PM] Biswas Sir Hod: How can they combine both? 

How many in the placebo group who just required hospitalization but didn't die?

[1/27, 10:17 PM] Chanku: The adverse effects like arrythmias and hypersensitive reaction numbers it's not clear sir.....

[1/27, 10:18 PM] Chanku: After these first 1 to 3 days, 5 of 1351 patients in the REGEN-COV 2400-mg group (0.4%), 5 of 735 patients in the REGEN-COV 1200-mg group (0.7%), 46 of 1340 patients in the placebo group who underwent randomization concurrently with the REGEN-COV 2400-mg group (3.4%), and 18 of 748 patients in the placebo group who underwent randomization concurrently with the REGEN-COV 1200-mg group (2.4%) had Covid-19–related hospitalization or died

[1/27, 10:23 PM] Biswas Sir Hod: Exactly! How can they equate hospitalization with death? 

How many among those got hospitalized and how many died?

[1/27, 10:23 PM] Biswas Sir Hod: Exactly! They are hiding

[1/27, 10:24 PM] Chanku: The ones who received placebo that is normal saline and the ones who received the drug, hypersensitivity causing interruption occured only in one each sir

[1/27, 10:25 PM] Chanku: I'll search for any other trial, others showed they have been funded by the company sir, I guess this one is too

[1/27, 10:27 PM] Biswas Sir Hod: 👆please all the above in the group so that the PG collating the monthly academic session can add the above conversations to this week's journal club

[1/27, 10:27 PM] Chanku: Ok sir

[1/27, 10:28 PM] Biswas Sir Hod: "Funding and Disclosures

Supported by Regeneron Pharmaceuticals, F. Hoffmann–La Roche, and the Biomedical Advanced Research and Development Authority of the Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response (contract number HHSO100201700020C)."

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