Compassionate Use of Remdesivir for Patients with Severe COVID-19

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Salient Points

The following article focuses on the use of remdesivir in the management of patients with severe COVID-19. Remdesivir was provided on a compassionate use basis for the management of patients with COVID-19. This report is based on the data from patients who received remdesivir during the period from January 2020 to March 2020.

Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving ECMO. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% among patients receiving invasive ventilation and 5% among those not receiving invasive ventilation.

From this cohort study it was observed that clinical improvement was observed in 36 out of 53 patients (68%).

Detailed Summary

Inclusion Criteria:

Approval of requests was reserved for hospitalized patients who had SARS-CoV-2 infection confirmed by RT-PCR assay and either an oxygen saturation of 94% or less while the patient was breathing ambient air or a need for oxygen support. In addition, patients were required to have a creatinine clearance above 30 ml per minute and serum levels of ALT and AST less than five times the upper limit of the normal range, and they had to agree not to use other investigational agents for Covid-19.

The planned treatment was a 10-day course of remdesivir, consisting of a loading dose of 200 mg intravenously on day 1, plus 100 mg daily for the following 9 days. Supportive therapy was to be provided at the discretion of the clinicians.

Follow-up was to continue through at least 28 days after the beginning of treatment with remdesivir or until discharge or death.

Data on patients’ oxygen-support requirements, adverse events, and laboratory values, including serum creatinine, ALT, and AST, were to be reported daily, from day 1 through day 10, and additional follow-up information was solicited through day 28.

The incidence of key clinical events were quantified, including changes in oxygen-support requirements (ambient air, low-flow oxygen, nasal high-flow oxygen, noninvasive positive pressure ventilation, invasive mechanical ventilation, and ECMO), hospital discharge, and reported adverse events, including those leading to discontinuation of treatment, serious adverse events, and death.

In addition, evaluation of the proportion of patients with clinical improvement, as defined by live discharge from the hospital, a decrease of at least 2 points from baseline on a modified ordinal scale, or both. The six-point scale consists of the following categories:

  1. Not hospitalized
  2. Hospitalized, not requiring supplemental oxygen
  3. Hospitalized, requiring supplemental oxygen
  4. Hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both.
  5. Hospitalized, requiring invasive mechanical ventilation, ECMO, or both
  6. Death.

Results

In total, 61 patients received at least one dose of remdesivir on or before March 7, 2020; 8 of these patients were excluded because of missing postbaseline information (7 patients) and an erroneous remdesivir start date. Of the 53 remaining patients included in this analysis, 40 (75%) received the full 10-day course of remdesivir, 10 (19%) received 5 to 9 days of treatment, and 3 (6%) fewer than 5 days of treatment.

Seven of the 53 patients (13%) died after the completion of remdesivir treatment, including 6 of 34 patients (18%) who were receiving invasive ventilation and 1 of 19 (5%) who were receiving noninvasive oxygen support. The median interval between remdesivir initiation and death was 15 days. Overall mortality from the date of admission was 0.56 per 100 hospitalization days and did not differ substantially among patients receiving invasive ventilation as compared with those receiving noninvasive ventilation. Risk of death was greater among patients who were 70 years of age or older and among those with higher serum creatinine at baseline. The hazard ratio for patients receiving invasive ventilation as compared with those receiving noninvasive oxygen support was 2.78. A total of 32 patients (60%) reported adverse events during follow-up.           The most common adverse events were:

  1. Increased hepatic enzymes
  2. Diarrhea
  3. Rash
  4. Renal impairment
  5. Hypotension

In general, adverse events were more common in patients receiving invasive ventilation. A total of 12 patients (23%) had serious adverse events. The most common serious adverse events — MOD, septic shock, acute kidney injury and hypotension were reported in patients who were receiving invasive ventilation at baseline.

Four patients (8%) discontinued remdesivir treatment prematurely: one because of worsening of preexisting renal failure, one because of multiple organ failure, and two because of elevated aminotransferases, including one patient with a maculopapular rash.

Reference Link : https://www.nejm.org/doi/full/10.1056/NEJMoa2007016

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