Remdesivir. Hydroxychloroquine apart, no drug during the current pandemic created as much controversy, generated as much hope, led to as much black marketing and eniced as many physicians and people as Remdesivir did. I was not sure if remdesivir indeed reduced the chances of dying in hospitalised patients and wondered if the hype and hope that the drug had triggered was indeed justified.
Here are my tweets on Remdesivir:
This is interesting.
— SP Kalantri (@spkalantri) June 1, 2021
Although Wardha district has stocked over 8000 vials of Remdesivir, there are no buyers. No more indents from local hospitals to the district remdesivir regulator.
Reason?
Now, the patients have begun questioning their doctors, "Why remdesivir?"
A medical college in Maharashtra achieves with #remdesivir what trialists- Wuhan, ACCT1 and Solidarity couldn't. Whopping success.
— SP Kalantri (@spkalantri) November 3, 2020
Hazards of media publicizing retrospective uncontrolled observational data.
The very reason why we need randomised controlled trials. pic.twitter.com/4HulitkZBp
If we ask the Covid scientific bodies & the state task forces to separate the wheat from the chaff, are we expecting too much?
— SP Kalantri (@spkalantri) May 30, 2021
⬆️Wheat- Dexa, Toci, Enoxaparin, Oxygen
⬇️Chaff- Remdesivir, Favipiravir, HCQ, Azithromycin, Doxycycline, Ivermectin, Plasma, 2DG, interferon α. Zinc
Does #remdesivir shorten hospital stay or improve survival among patients with Covid19?
— SP Kalantri (@spkalantri) July 19, 2021
No. Contrary to widely held perception, it does neither.
I summarise JAMA 15 July 2021 study in a PP slide. pic.twitter.com/PaXjzsAXh3
#Covid19. What works and what doesn't. My impressions- based on EBM. #Remdesivir, following Solidarity trial should receive a red signal- let me think… pic.twitter.com/UYWs6QGMgn
— SP Kalantri (@spkalantri) October 25, 2020
They came, they saw, they went. Or did they?
— SP Kalantri (@spkalantri) July 18, 2021
Hydroxychloroquine, Favipiravir, Azithromycin, Doxycycline, Itolizumab, Ivermectin, Remdesivir, Convalescent plasma, Vitamin D, 2-DG, Zinc.
Ineffective therapies against #Covid19.
Now that #Remdesivir has been shown not to benefit hospitalized Covid19 patients, how shall we justify spending Rs 30,000 for a therapy which doesn't work.
— SP Kalantri (@spkalantri) October 16, 2020
Eye-opening numbers, these. #Solidarity trial. Of the 2743 patients on #remdesivir, 301 died. Of the 2708 patients on usual care, 303 died. 11.0% vs.11.2%.
— SP Kalantri (@spkalantri) October 16, 2020
We don't have to calculate P values to assess difference between 2 groups.
Now, the sole savior is #dexamethasone.
Five new therapies have caught the fancy of physicians, worldwide, for the treatment of mild-moderately ill, at-risk outpatients with Covid19.
— SP Kalantri (@spkalantri) January 2, 2022
Which drug to use? I have summarised the efficacy of each drug— #Paxlovid, #Sotrovimab, #Remdesivir, #Molnupiravir and #Fluvoxamine. pic.twitter.com/MLUROBfOKw
A journalist who never spoke to me or wrote me a email nor texted a query, misquotes me on irrational use of #Remdesivir among Covid19 patients in India, gets my designation wrong and misplaces the location of the institute where I work. @IndiaToday please correct. pic.twitter.com/ilSYZFXHIm
— SP Kalantri (@spkalantri) October 11, 2020
Last week, our residents noted two cardiac adverse events following #Remdesivir administration: severe bradycardia (heart rate dipping below 40) and abnormal cardiac rhythm. They had to stop the drug halfway through.
— SP Kalantri (@spkalantri) May 24, 2021
Primum non nocere.
Not out! Roared FDA today, as it approved #remdesivir for Covid19 barely a week after #Solidarity trial concluded that it doesn't work.
— SP Kalantri (@spkalantri) October 23, 2020
Politics getting the better of Science. pic.twitter.com/DJwIWxLwEg
Two lines appeared on the Survival Curve, and I—
— SP Kalantri (@spkalantri) December 3, 2020
I took the one supposed to make few patients die,
Alas! The line I chose made no difference at all.#Remdesivir in Covid19
Apologies Robert Frost pic.twitter.com/RqXPtNhjCC
Biocon (#itolizumab) could achieve what RECOVERY (#dexamethasone) and NIAID (#Remdesivir) couldn't.
— SP Kalantri (@spkalantri) July 28, 2020
Zero mortality.
This is what ICU physicians aim at, patients pray for & funders pay for. But their wishes seldom come true.
What more could we ask for! Truly a magic bullet. pic.twitter.com/nGu473TgvM
#Dexamethasone and #Remdesivir. In COVID19 pneumonia. The former is cheap, widely available and familiar. The later is expensive, in short supply and relatively unknown.
— SP Kalantri (@spkalantri) August 23, 2020
We need to know if remdesivir offers added benefit—early recovery and fewer deaths—over dexamethasone.
For almost 5 months, #Remdesivir ruled the roost. It fascinated physicians, enchanted patients, allured policymakers, enticed taskforce members and casted a spell on politicians.
— SP Kalantri (@spkalantri) October 17, 2020
How can it leave the hospitals—unsung, unwept?
How many patients will rush to buy #remdesivir if their doctors tell them, "this drug will cost you Rs 24,000 and will only reduce your hospital stay by 4 days but won't reduce chances of dying from #Covid_19."
— SP Kalantri (@spkalantri) July 10, 2020
They might say yes. Fuelled by fear; fanned by Pharma.
Even before the ink on DGHS recommendations— several warnings on the use of Remdesivir in patients with Covid19— could dry, the GST council today reduced GST on remdesivir from 12% to 5%.
— SP Kalantri (@spkalantri) June 12, 2021
What was the rationale for lowering the cost of a not-so-useful Covid drug?
When do we expect the @MoHFW_INDIA to revise the clinical management protocol for #Covid19?
— SP Kalantri (@spkalantri) December 3, 2020
HCQ, Remdesivir and Plasma continue to fancy the policymakers, despite evidence to the contrary. pic.twitter.com/1VGTv2J3vG
What if #COVID19 patients in the ICU get #Remdesivir, #dexamethasone, #tocilizumab, and #Plasma but the ICU lacks enough skilled and motivated nurses and doctors to care for them?
— SP Kalantri (@spkalantri) July 27, 2020
The mortality numbers won't go down- they might go up.
A fortnight ago, the Maharashtra public health dept expanded the indication for #Remdesivir – it may be used with informed consent in patients with:
— SP Kalantri (@spkalantri) October 17, 2020
1⃣high index of suspicion of #COVID19 and
2⃣negative RTPCR and
3⃣CT severity index >9.
Time to revise the recommendation? pic.twitter.com/jKQBm4GMWC
Today's @NEJM concludes that none of the 4 antivirals has any benefit in hospitalized Covid19. The strength of the trial lies in its design and numbers: RCT in 405 hospitals, 30 countries, 11,330 adults. #Remdesivir, one of the most hyped drugs, failed. pic.twitter.com/A6fDtTrQ3S
— SP Kalantri (@spkalantri) December 3, 2020
Hydroxychloroquine, Favipiravir, Convalescent Plasma, Remdesivir, Ivermectin, Azithromycin, Vitamins… have they gone for good, or shall they rise from the ashes as the third wave arrives?#Covidmyopia
— SP Kalantri (@spkalantri) August 9, 2021
The mortality rates in the 3 #Remdesivir clinical trials for #COVID19 show striking variation.
— SP Kalantri (@spkalantri) August 22, 2020
How do we explain these varying rates? #Lancet #NEJM #JAMA pic.twitter.com/7KFPr9cMnT
The @JAMAInternalMed trial on #Remdesivir in COVID pneumonia is not double blind.
— SP Kalantri (@spkalantri) August 23, 2020
Why?
"Treatment was open label because the sponsor had an insufficient number of placebo-containing vials to support this trial."
Easy to fund Remdesivir but difficult to procure placebo vials?
#Solidarity trial also tells us that patients had a 1 in 50 chance of dying if they didn’t need oxygen; the probability increased to 1 in 8 in those on low/high flow oxygen and 2 in 5 for those on ventilator. #Remdesivir failed to improve these numbers.
— SP Kalantri (@spkalantri) October 16, 2020
When VIPs get admitted to the hospital and insist for 3-day #remdesivir therapy, they put physicians, residents, interns, nurses, technicians, social workers and orderlies at risk of contracting #Omicron.
— SP Kalantri (@spkalantri) January 5, 2022
Not to speak of risk to other non-Covid patients in the hospital.
I am impressed by the narrow 95% confidence intervals in the #Solidarity trial. Quite close to point estimates. By contrast, both Wuhan and #ACCT trials on Remdesivir generated wide CIs.
— SP Kalantri (@spkalantri) October 16, 2020
The sample size matters.
Although research contradicts common medical therapies, patients want them, physicians prescribe them and FDAs keeps on approving unproven therapies.
— SP Kalantri (@spkalantri) October 23, 2020
In this pandemic we not only have to fight the virus but also outbreak of unnecessary & unhelpful treatments.#remdesivir #EBM
#recovery and #Solidarity trials could enroll thousands of participants for their #COVID19 trials. So did Remdesivir trialists in NIH and Wuhan. In just 8 weeks.
— SP Kalantri (@spkalantri) July 12, 2020
India recorded 850000 COVID cases & 22500 deaths. Why Indian trials have such appalling numbers as 30, 100, and 120?
The #Remdesivir study reminds us of the history of medicine- a good chunk of current medical practice gets reversed over time.
— SP Kalantri (@spkalantri) October 20, 2020
Some drugs last for years before they are called off. Some linger on for a few months before they beat a hasty retreat.
One Step Forward. Two Steps Back. @NEJM 2 Dec carries a clinical trial, a perspective and an editorial on the efficacy of #Remdesivir in Covid19.
— SP Kalantri (@spkalantri) December 3, 2020
The concluding sentence of the edit describes the confusion antivirals have generated. pic.twitter.com/Wiblv0q6jd
The @nppa_india says that it cannot notify #Remdesivir as a drug. So, it cannot regulate its price, either.
— SP Kalantri (@spkalantri) July 30, 2020
During a pandemic, people will have to pay through their nose for a drug, that at best improves their recovery time by 4 days. Strange helplessness.#healtheconomics
Should doctors admit mildly ill Covid+ patients to the hospital for three-day intravenous infusion of #remdesivir and put at risk non-Covid patients and hospital staff from contacting #Omicron?
— SP Kalantri (@spkalantri) January 5, 2022
Risk of tranmission overweighs possible benefits.
“New treatments are a bit like the proverbial new kid on the block: they have an allure that is hard to resist.” So wrote Friedman a decade ago.
— SP Kalantri (@spkalantri) October 17, 2020
How True!
Could this explain the obsessive infatuation of the medical communities with #Hydroxychloquine and #Remdesivir?
In higher risk groups, patients receiving #Remdesivir in #Solidarity trial ran a numerically higher risk of dying compared to those on usual care. The difference was not statistically significant, though.
— SP Kalantri (@spkalantri) October 16, 2020
Mortality 30.6% vs. 25%, Death Rate Ratio 1.16 ( 95% CI, 0.85-1.60).
What do 2 clinical trials, 1300 patients, published in @TheLancet and @NEJM tell us about #Remdesivir?
— SP Kalantri (@spkalantri) August 7, 2020
1⃣May be effective in reducing the time to recovery.
2⃣Might reduce deaths.
3⃣Has no effect on need for ventilation.
4⃣Has no effect on length of stay.
Weak recommendations.
In the 5 recent trials designed to test the efficacy of #COVID19 drugs— #Paxlovid, #Sotrovimab, #remdesivir, #Molnupiravir and #Fluvoxamine— for mild to moderately ill, at-risk Covid patients, of the 4849 patients, 34 died(in both arms of the study).
— SP Kalantri (@spkalantri) January 7, 2022
7 deaths per 1000 patients. pic.twitter.com/C6cJF87CNe
1. The 22 Dec @NEJM study paints #Remdesivir with rich and bright colours—making one believe that the drug works wonderfully well in infected outpatients at high risk for severe Covid19.
— SP Kalantri (@spkalantri) December 23, 2021
2. Let me summarise the important limitations of the trial.
— SP Kalantri (@spkalantri) December 23, 2021
First, the inclusion criteria. Because only 2.5% of the study patients were Asians, we cannot generalize these data to the Asians. Of note, Remdesivir did not work in the Hispanic population in this study.
3. Participants were excluded if they were receiving or were expected to receive supplemental oxygen at the time of screening.
— SP Kalantri (@spkalantri) December 23, 2021
Patients were also ineligible if they had received a SARS-CoV-2 vaccine. This criterion alone would exclude a large number of patients.
4. The last patient was enrolled on April 8, 2021—before the #Delta variant of SARS-CoV-2 emerged as the dominant circulating strain. Can we apply the study results to the delta or Omicron variants?
— SP Kalantri (@spkalantri) December 23, 2021
5. 1 of 20 patients who received Remdesivir was spared hospitalization. Looks impressive but note that no patient died in either group by day 28, an important outcome measure. The 2 lines in the Kaplan–Meier graph do diverge, but we must read between the lines.
— SP Kalantri (@spkalantri) December 23, 2021
6. The most common adverse events in both groups were nausea, headache, and cough. These are classical Covid symptoms—what made the researchers label them as the adverse events?
— SP Kalantri (@spkalantri) December 23, 2021
7. Despite its perceived efficacy, remdesivir failed to reduce the upper airway viral load. This contrasts with monoclonal antibodies #molnupiravir, both of which reduce viral burden rapidly.
— SP Kalantri (@spkalantri) December 23, 2021
8. And there is a practical challenge. Only a sixth of study patients received infusion at home. How do we ensure home-based access of Remdesivir to an infected person in resource limited setting?
— SP Kalantri (@spkalantri) December 23, 2021
9. Researchers have faced huge problems in injecting single-dose monoclonal AB—how can we identify, infuse the drug and monitor outpatients for a 3-day outpatient intravenous remdesivir therapy?
— SP Kalantri (@spkalantri) December 23, 2021
10. The trial had to be stopped half way through because there were ethical concerns regarding assigning patients to when the vaccination rates rose and monoclonal antibodies became available. These issues are much more relevant today than in early 2021.
— SP Kalantri (@spkalantri) December 23, 2021
11. Authors plead that outpatient remdesivir could serve vaccine-naïve persons. In resource limited settings, can those who are unable to access vaccine access remdesivir? Bread vs Cake?
— SP Kalantri (@spkalantri) December 23, 2021
12.The authors selectively hype ACTT-1 and SIMPLE trials and downplay Wuhan and the WHO Solidarity trial.
— SP Kalantri (@spkalantri) December 23, 2021
So, a pharma sponsored trial. Trying to thrust Remdesevir back into the limelight. Much ado about nothing? END.
An oral drug with few drug–drug interactions and a good safety profile.#Baricitinib. Janus Kinase Inhibitor.
— SP Kalantri (@spkalantri) December 14, 2020
When combined with #Remdesivir , the combo slightly speeds up #COVIDー19 recovery time.
My visual summary of the 11 Dec @NEJM trial. pic.twitter.com/KR42UbxzF6
Days are not far when we shall see #Paxlovid /Ritonavir+ #Molnupiravir+ Monoclonal Antibodies+ #Remdesivir combo used to treat Covid+ high risk individuals.
— SP Kalantri (@spkalantri) January 1, 2022
Using four drugs to treat a mildly ill Covid+ patient—this would not only be irrational but also a dreadful idea.
The @JAMA_current study compared 5-day and 10-day remdesivir course with standard care in COVID19 pneumonia.
— SP Kalantri (@spkalantri) August 23, 2020
5-day benefitted; 10-day didn’t.
But, the median treatment length was 5 vs 6 days in the two arms of the study. 1/2
Thus, with one additional day of treatment length— just one more #Remdesivir injection—the 10-day arm loses the statistical significance. The clinical status doesn't improve.
— SP Kalantri (@spkalantri) August 23, 2020
What do we make out from this? How should the physicians apply this study at the point of care? 2/2
Let me clarify that based on NEJM 22 May rigorously designed and conducted clinical trial on #Remdesivir (shorter time to recovery- 15 vs 11 days) we have been using the drug for hypoxic Covid19 inpatients in our hospital.
— SP Kalantri (@spkalantri) October 11, 2020
I never said that the drug is unproven. @IndiaToday
Might #Remdesivir help us fight the #Omicron? Patients often ask us.
— SP Kalantri (@spkalantri) January 14, 2022
For a 3-day intravenous course, they would need to travel and get admitted to the hospital—increasing their burden as well as risking the health professions.
Are the benefits worth the risk and trouble?
Should the results of drug trials in Covid19 be shared with media before the peer reviewed manuscripts are published in medical journals?
— SP Kalantri (@spkalantri) July 10, 2021
In an era of fast publication, ACTT Remdesivir trialists enrolled last patient on 19 Apr 2020 & published the trial in @NEJM 4 weeks later.
Which #COVID19 patients are most likely to benefit from #baricitinib plus #remdesivir combination?
— SP Kalantri (@spkalantri) December 15, 2020
Those on high-flow oxygen.
How quickly might they recover? Median time to recovery 10 days. Patients receiving the usual care take 18 days.
The @NEJM 11 Dec clinical trial. pic.twitter.com/sKzUAfy253
#Dengue bears an uncanny resemblance to #COVID19 – fear, panic and uncertainty in public; overemphasis on monitoring tests and overtreatment by physicians.
— SP Kalantri (@spkalantri) July 31, 2021
Earlier it was clamour for Remdesivir; now there is clamour for platelets.
Should we have a randomized, double-blind, head to-head comparison of
— SP Kalantri (@spkalantri) December 15, 2020
🚻Baricitinib + #Remdesivir
with
🚻#Dexamethasone + Remdesivir
To find out the efficacy and safety of the two anti-inflammatory drugs for #COVID19.
Or should we take off remdesivir from both trials?
#HCQ, Remdesivir, Plasma, #Favipiravir, Coronil, #vaccines—almost all anti-COVID drugs have generated cytokine storms—fierce and frightening—among media and public. #Coronavirus should take a leaf out of social media whenever it invades the human body.
— SP Kalantri (@spkalantri) July 4, 2020
O #Remdesivir , where is thy sting?
— SP Kalantri (@spkalantri) December 3, 2020
O #Hydroxychloroquine , where is thy victory? @NEJM WHO Solidarity Trial on antivirals.
