PETAL Network trial included nearly 500 hospitalized patients

Yet another study — this one from the National Heart, Lung, and Blood Institute PETAL Clinical Trials Network — found no benefit for hydroxychloroquine in the treatment of patients hospitalized with Covid-19.

PETAL researchers randomized nearly 500 patients with Covid-19 being treated at 34 U.S. hospitals to receive either hydroxychloroquine or placebo, but the trial was stopped early for futility.

The researcher concluded that treatment with hydroxychloroquine neither improved nor worsened clinical outcomes among adults hospitalized for respiratory illness from Covid-19. Their findings were published online Nov. 9 in JAMA.

“These findings were consistent in all subgroups and for all outcomes evaluated, including an ordinal scale of clinical status, mortality, organ failures, duration of oxygen use, and hospital length of stay,” wrote Wesley H. Self, MD, of Vanderbilt University Medical Center, Nashville, and colleagues.

In an editorial accompanying the study, infectious disease researcher Michael S. Saag, MD, of the University of Alabama at Birmingham, noted that the PETAL network study joins a growing number of rigorous, well-conducted clinical trials finding no benefit for hydroxychloroquine as a treatment for Covid-19.

“This raises the question: How did medicine get to the point where so many studies were conducted assessing the possible benefit of hydroxychloroquine, that led to nearly identical findings, and have been published in major journals?” he asked.

While noting that small, early trials suggesting a benefit played a role, along with “the desperation of clinicians who were providing care for patients with a potentially fatal disorder for which there was not treatment,” Saag concluded that the “politicization of the treatment was a more important factor in promoting interest in the use of this drug.”

Saag recalled that in early April, President Donald Trump, “speaking on gut instinct, promoted the drug as a potential treatment.”

Around this time, the president also authorized the U.S. government to purchase and stockpile 29 million hydroxychloroquine doses for use in patients with Covid-19, the FDA issued an Early Use Authorization for this purpose, and use of the drug increased dramatically in U.S. hospitals, despite the fact that no health officials in the U.S. government endorsed this practice “owing to the absence of robust data and concern about adverse effects,” Saag wrote.

“These events sparked an avalanche of studies, many of which are now completed and are being reported in the scientific literature. These well-conducted trials… demonstrate the lack of efficacy of hydroxychloroquine in patients with Covid-19,” Saag wrote.

“In a twist of irony, the U.S. president did not receive hydroxychloroquine, with or without azithromycin, when he contracted Covid-19 and was hospitalized at Walter Reed National Military Medical Center in early October,” he added.

The blinded, placebo-controlled randomized PETAL network trial included patients hospitalized for Covid-19, who were enrolled from April 2 through June 19, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients was enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients.

Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237), and the primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities).

For the primary outcome, there was no significant difference between the hydroxychloroquine and placebo groups (median [interquartile range] score, 6 [4-7] vs 6 [4-7]; adjusted odds ratio, 1.02; 95% CI, 0.73-1.42).

None of the 12 secondary outcomes were significantly different between groups, including mortality at 28 days, which was 10.4% in the hydroxychloroquine group versus 10.6% in the placebo group (absolute difference, −0.2%; 95% CI, −5.7% to 5.3%: adjusted odds ratio, 1.07; 95% CI, 0.54- 2.09).

In his editorial, Saag wrote that among the lessons to be learned from the hydroxychloroquine saga are that findings from a single, non-randomized study and case reports must be considered preliminary and not actionable, and that patients with a life-threatening disease and few treatment options “will accept any treatment, especially when such treatment is promoted by individuals who ordinarily should be trusted, such as the U.S. president.

“The clear, unambiguous and compelling lesson from the hydroxychloroquine story for the medical community and the public is that science and politics do not mix,” Saag wrote. “Science, by definition, requires diligence and an honest assessment of findings; politics not so much. The number of articles in the peer-reviewed literature over the last several months that have consistently and convincingly demonstrated the lack of efficacy of a highly hyped ’cure’ for Covid-19 represents the consequence of the irresponsible infusion of politics into the world of science evidence and discourse. For other potential therapies or interventions for Covid-19 (or any other diseases), this should not happen again.”

  1. Another large, randomized trial found no benefit for the use of hydroxychloroquine as a treatment for severe Covid-19.
  2. Researchers concluded that treatment with hydroxychloroquine neither improved or worsened clinical outcomes among adults hospitalized with respiratory illness from Covid-19.

Salynn Boyles, Contributing Writer, BreakingMED™

This research was funded by the National Heart, Lung and Blood Institute and the Harvard Catalyst/Harvard Clinical and Translational Science Center.

Researcher Wesley H. Self reported receiving grants from NHLBI and personal fees from Aerpio Pharmaceuticals unrelated to this study.


Cat ID: 190

Topic ID: 79,190,254,930,730,933,190,926,192,927,151,928,925,934