RCT: Failed benefit by both Remdesvir and convalescent plasma in RCT

[Prasanta R. Mohapatra]

Dear ALL

Both treatment options  with RCT are available but not promising , The treatments must guide us better way.

 

 

1. Unfortunately Emergency Approval of Blood Plasma Is Now on Hold by FDA(“convalescent plasma has not yet been shown to be safe and effective as a treatment for COVID-19.”)
2. Since the Emergency Use Authorization was granted, there has been a huge demand for remdesivir from both patients and physicians, generating considerable debate over how to ensure adequate, equitable, and affordable access but newest trial :  difference was of uncertain clinical importance.

Therefore finding other antiviral drug or a vaccine is the only route for survival against it. 

 

Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19 :A Randomized Clinical Trial

JAMA. Published online August 21, 2020. doi:10.1001/jama.2020.16349 

Key Points

Question  Does remdesivir provide a benefit on clinical status for patients hospitalized with moderate coronavirus disease 2019 (COVID-19) pneumonia?

Findings  In this randomized, open-label, phase 3 trial that included 584 patients with moderate COVID-19, the day 11 clinical status distribution measured on a 7-point ordinal scale was significantly better for those randomized to a 5-day course of remdesivir (median length of treatment, 5 days) compared with those randomized to standard care. The difference for those randomized to a 10-day course (median length of treatment, 6 days) compared with standard care was not significantly different.

Meaning  Hospitalized patients with moderate COVID-19 randomized to a 5-day course of remdesivir had a statistically significantly better clinical status compared with those randomized to standard care at 11 days after initiation of treatment, but the difference was of uncertain clinical importance.

Other 2 trials on remdesivir

 

Wang  Y, Zhang  D, Du  G,  et al.  Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial.   Lancet. 2020;395(10236):1569-1578. doi:10.1016/S0140-6736(20)31022-9PubMedGoogle ScholarCrossref

Results : failed to show benefit but recruited only 237 patients 

Beigel  JH, Tomashek  KM, Dodd  LE,  et al; ACTT-1 Study Group Members.  Remdesivir for the treatment of Covid-19—preliminary report.   N Engl J Med. Published online May 22, 2020. doi:10.1056/NEJMoa2007764PubMedGoogle Scholar

Results :10-day course of remdesivir had a recovery time that was shorter by 4 days (median, 11 vs 15 days) compared with placebo.³ No significant difference was found in mortality between drug (7.1%) and placebo (11.9%) (hazard ratio, 0.70; 95% CI, 0.47-1.04).

 

Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19A Randomized Clinical Trial

JAMA. 2020;324(5):460-470. doi:10.1001/jama.2020.10044

Key Points

Question  What is the effect of convalescent plasma therapy added to standard treatment, compared with standard treatment alone, on clinical outcomes in patients with severe or life-threatening coronavirus disease 2019 (COVID-19)?

Finding  In this randomized clinical trial that included 103 patients and was terminated early, the hazard ratio for time to clinical improvement within 28 days in the convalescent plasma group vs the standard treatment group was 1.40 and was not statistically significant.

Meaning  Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment did not significantly improve the time to clinical improvement within 28 days, although the trial was terminated early and may have been underpowered to detect a clinically important difference.

 

Available Evidence for Convalescent Plasma Therapy (as on 21.8.2020)

3. “convalescent plasma has not yet been shown to be safe and effective as a treatment for COVID-19.”

https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-process-cber/recommendations-investigational-covid-19-convalescent-plasma

 

4. Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19 A Randomized Clinical Trial. doi:10.1001/jama.2020.10044   Clinical Trial Registry: ChiCTR2000029757

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270883/

Conclusion and Relevance: “Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference.”

 

5. Conclusion from metanalysis: “Studies of non-COVID-19 severe respiratory viral infections provide indirect, very low-quality evidence that raises the possibility that convalescent plasma has minimal or no benefit in the treatment of COVID-19 and low-quality evidence that it does not cause serious adverse events.” https://pubmed.ncbi.nlm.nih.gov/32444482/

 

6. F.D.A.’s Emergency Approval of Blood Plasma Is Now on Hold

https://www.nytimes.com/2020/08/19/us/politics/blood-plasma-covid-19.html

 

7. We are very uncertain whether convalescent plasma is beneficial for people admitted to hospital with COVID-19. https://pubmed.ncbi.nlm.nih.gov/32648959/

Cochrane Database Syst Rev. 2020 Jul 10;7(7):CD013600. (Efficacy and safety of convalescent plasma for severe COVID-19 based on evidence in other severe respiratory viral infections: a systematic review and meta-analysis)

 

8. “other treatments were also administered to the patients and as a result data are difficult to interpret”

https://pubmed.ncbi.nlm.nih.gov/32584322/

 

9. Status in India (phase-II clinical trial) Too early to comment, not even phase-III stage

https://www.icmr.gov.in/pdf/covid/techdoc/PLACID_List_17062020.pdf

 

 

[Debasish Hota]

Dear Prashant,

Thanks for the article.

So far, except for Dexamethasone, none of the drugs have shown any significant difference in reducing disease severity, hospital stay, other parameters of clinical improvement OR mortality.

When no specific or effective drug is available, physicians emotions get high, they prescribe whatever is made available to them. 

But the real difference comes from the data from larger sample.

So far, we care as usual, but are as helpless as before..

Thanks

 

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[Prasanta R. Mohapatra]

True,

There are lot of advertisements for Remdesvir & C Plasma therapy and so on..., practically we have 3 proven treatment options(depending on severity)  : 1. Oxygen, 2. Corticosteroid 3. LMWH/NOAC in addition to infection control, treatment of comorbidities and best supportive care.

Regards

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