High-dose chloroquine trial for COVID-19 halted due to increased fatality rates
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An international group of researchers terminated a safety and efficacy phase 2b trial of higher dose chloroquine as a treatment for patients with COVID-19 early after observing increased safety hazards and fatality rates.
“Currently, there is no specific antiviral therapy recommended for coronavirus infections. Few treatment studies have been carried out because most strains of human coronavirus cause self-limiting disease and routine supportive care is usually effective. For past severe strains of coronavirus, outbreaks were scattered, thus not allowing timely clinical trials,” Mayla Gabriela Silva Borba, of Universidade do Estado do Amazonas, and colleagues wrote. “Recent publications have drawn attention to the possible benefit of chloroquine sulphate and phosphate salts (chloroquine diphosphate [CQ]) and hydroxychloroquine (HCQ) for the treatment of [patients with] SARS-CoV-2.”
Borba and colleagues conducted a parallel, double-blinded, randomized phase 2b clinical trial of hospitalized patients aged 18 years and older with a respiratory rate greater than 24 respirations per minute and/or the following: heart rate higher than 125 beats per minute, in the absence of a fever; peripheral oxygen saturation below 90% in ambient air; and/or shock, classified as mean arterial pressure lower than 65 mmHg, with the need for vasopressors medicines or oliguria or a lower level of consciousness. They aimed to assess the safety and efficacy of two different CQ dosages as adjunctive therapy in patients with confirmed, severe COVID-19.
According to the study, 81 eligible participants received either high-dose CQ (600 mg CQ twice daily for 10 days or a total dose of 12 g; n = 41) or low-dose CQ (450 mg for 5 days, twice daily only on the first day, or a total dose of 2.7 g; n = 40) orally or through a nasogastric tube, along with ceftriaxone and azithromycin.
The 81 participants were enrolled from a predefined sample size of 440 patients. Results of the trial showed that the high-dose CQ arm more often led to a corrected QT greater than 500 ms (25%) and resulted in a trend toward higher lethality (17%) than the lower dosage. According to the study results, the fatality rate was 13.5% (95% CI, 6.9%-23%), which overlaps with the confidence interval seen in historical data from similar patients who were not taking CQ (95% CI, 14.5%-19.2%).
“Preliminary findings suggest that the higher CQ dosage (10-day regimen) should not be recommended for COVID-19 treatment because of its potential safety hazards. Such results forced us to prematurely halt patient recruitment to this arm,” the authors wrote. “Given the enormous global push for the use of CQ for COVID-19, results such as the ones found in this trial can provide robust evidence for updated COVID-19 patient management recommendations.”
The authors suggest that future trials examine the role of CQ or HCQ as a prophylactic drug, as well as trials that assess its efficacy against progression to severity when given to patients with mild or moderate disease.
“Even if we fail to generate good evidence in time to control the current pandemic, the information will highly impact the way we deal with next coronavirus outbreaks in the future,” Borba and colleagues concluded. – by Caitlyn Stulpin
Disclosures: Borba reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.
Reference:
Borba MGS, et al. medRxiv. 2020;doi:10.1101/2020.04.07.200564.
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