New double-blind RCT from India published - Zero mortality in treatment group, however no difference as to other primary & secondary outcomes (2021-01-10)

ktrss89 | 11 points | Jan 10 2021 10:50:21

New double-blind RCT from India published - Zero mortality in treatment group, however no difference as to other primary & secondary outcomes (2021-01-10)

Seems well-designed on first view. No significance difference as to: negative RT-PCR status on day 6, symptom status on day 6, discharge status on day 10, admission to ICU or invasive mechanical ventilation, but zero mortality in treatment group showing statistical significance. Invasive mechanical ventilation is also trending towards statistical significance (p value=0.088).

Posting the abstract below.

Objective: Ivermectin has been suggested as a treatment for COVID-19.This randomised control trial was conducted to test the efficacy of Ivermectin in the treatment of mild and moderate COVID-19.

Design: Parallel, double blind, randomised, placebo controlled trial

Setting: A tertiary care dedicated COVID-19 hospital in Bihar, India Participants: Adult patients ( 18 years) admitted with mild to moderate COVID 19 disease (saturation 90% on room air, respiratory rate < 30 and no features of shock) with no contraindications to ivermectin and willing to participate in the study

Intervention: Patients in the intervention arm were given ivermectin 12 mg on day 1 and day 2 of admission. Patients in the placebo arm were given identical looking placebo tablets. Rest of the treatment was continued as per the existing protocol and the clinical judgment of the treating teams.

Outcome Measures: The primary outcome measure was a negative RT-PCR test for SARS-CoV-2 on day 6 of admission. The secondary outcome measures were symptom status on day 6, discharge status on day 10, admission to ICU, need for invasive mechanical ventilation and in-hospital mortality. Results: A total of 115 patients were enrolled for the study of which 112 were included in the final analysis. Of them, 55 were randomised to the intervention arm while 57 were randomised to the placebo arm. There was no significant difference in the baseline characteristics of the two arms. There was no significant difference in the primary outcome, i.e. negative RT-PCR status on day 6 between the two groups. Similarly, there was no significant difference between the two groups in most of the secondary outcome measures, viz. symptom status on day 6, discharge status on day 10, admission to ICU, and need for invasive mechanical ventilation. However, while there was no in-hospital mortality in the intervention arm, there were 4 deaths in the placebo arm. As a result, all patients in the intervention arm (n=56) were successfully discharged as compared to 93.1% (n=54/58) in the placebo arm (RR 1.1, 95% CI 1.0 to 1.2, p=0.019).

Conclusion: There was no difference in the primary outcome i.e. negative RT-PCR status on day 6 of admission with the use of ivermectin. However, a significantly higher proportion of patients were discharged alive from the hospital when they received ivermectin.

[-] akaariai | 2 points | Jan 10 2021 11:34:51

Very interesting results - higher viral clearance in placebo group(!), 23.6% vs 31.6% by day 6 by RT-PCR test. Higher discharge rate by day 10 for IVM 80% vs 73.7%. And as said only significant result is less mortality for ivm.

Link to study: https://www.medrxiv.org/content/10.1101/2021.01.05.21249310v1.full.pdf+html

[-] ktrss89 | 2 points | Jan 10 2021 11:43:40

The RT-PCR is only picking up RNA, not infectious virus, so I am not sure how important this endpoint is.

[-] ClasseD-48 | 1 points | Jan 11 2021 05:28:21

One thing that's important to remember is that after 8-9 days of symptoms, PCR swabs cannot be used to create viral cultures. What this means is that, in all likelihood, the viral phase ends after 8-9 days of symptoms. After that, PCR tests detect dead viruses.

Also take into consideration people are hospitalized usually after 7 days of symptoms.

Add the two together and the rational conclusion is most people are hospitalized at the END of the viral phase, when their body is ALREADY getting rid of all the virus. Antiviral treatments at that point are in all likelihood going to fail, not because they have no antiviral effect, but because the virus is already mostly dead. Even strong antivirals like remdesivir have been found to have no effect on hospitalized patients... frankly, even trying antiviral treatments on hospitalized patients is probably a waste of time. Can't have antiviral activity if there is no viral activity.

Maybe on severe COVID cases in immunosuppressed patients, the viral phase lasts longer and antiviral treatments could be useful, but this is about mild and moderate cases (at admission).

If ivermectin is still useful at that point, it must be due to anti-inflammatory effects.

[-] Haitchpeasauce | 1 points | Jan 11 2021 11:41:28

As I mentioned elsewhere the study doesn't say how long the patients had symptoms for before presenting at the hospital. They were given steroids on day 1 of admission which I think is a huge confounder, especially if this was given during the peak viral load phase.