On Saturday, April 11, the Arlington, Va.-based Infectious Diseases Society of America, the nationwide association representing infectious diseases specialists, epidemiologists, and other healthcare and scientific professionals, published a set of guidelines for the treatment of COVID-19 cases, at a time when clinician leaders are just beginning to solidify their understanding of COVID-19 treatment options. Its recommendations on the administration of hydroxychloroquine—with or without the addition of azithromycin—include the very strong qualifier that the panel’s members believe the unproven drug should be administered as part of participation in clinical trials.
The document’s executive summary reads thus:
“COVID-19 is a pandemic with a rapidly increasing incidence of infections and deaths. Many pharmacologic therapies are being used or considered for treatment. Given the rapidity of emerging literature, IDSA felt the need to develop living, frequently updated evidence-based guidelines to support patients, clinicians and other health-care professionals in their decisions about treatment and management of patients with COVID-19.
Summarized below are the recommendations with comments related to the clinical practice guideline for the treatment and management of COVID-19. A detailed description of background, methods, evidence summary and rationale that support each recommendation, and research needs can be found online in the full text. In brief, per GRADE methodology, recommendations are labeled as “strong” or “conditional”. The word “recommend” indicates strong recommendations and “suggest” indicates conditional recommendations. In situations where promising interventions were judged to have insufficient evidence of benefit to support their use and with potential appreciable harms or costs, the expert panel recommended their use in the context of a clinical trial. The guideline panel used the word “only” in recommendations about therapeutic agents with higher uncertainty and/or more potential for harm. These recommendations acknowledge the current “knowledge gap” and aim at avoiding premature favorable recommendations for potentially ineffective or harmful interventions.
Recommendation 1. Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends hydroxychloroquine/chloroquine in the context of a clinical trial. (Knowledge gap)
Recommendation 2. Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends hydroxychloroquine/chloroquine plus azithromycin only in the context of a clinical trial. (Knowledge gap)
Recommendation 3. Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends the combination of lopinavir/ritonavir only in the context of a clinical trial. (Knowledge gap)
Recommendation 4. Among patients who have been admitted to the hospital with COVID-19 pneumonia, the IDSA guideline panel suggests against the use of corticosteroids. (Conditional recommendation, very low certainty of evidence)
Recommendation 5. Among patients who have been admitted to the hospital with ARDS due to COVID-19, the IDSA guideline panel recommends the use of corticosteroids in the context of a clinical trial. (Knowledge gap)
Recommendation 6. Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends tocilizumab only in the context of a clinical trial. (Knowledge gap)
Recommendation 7. Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends COVID-19 convalescent plasma in the context of a clinical trial. (Knowledge gap)
The panel expressed the overarching goal that patients be recruited into ongoing trials, which would provide much needed evidence on the efficacy and safety of various therapies for COVID-19. The panel determined that when an explicit trade-off between the highly uncertain benefits and the known putative harms of these therapeutic agents were considered, a net positive benefit was not reached and could possibly be negative (risk of excess harm). The panel acknowledges that enrolling patients in RCTs might not be feasible for many frontline providers due to limited access and infrastructure. Should lack of access to clinical trials exist, we encourage setting up local or collaborative registries to systematically evaluate the efficacy and safety of drugs to contribute to the knowledge base. Each clinician can play a role in advancing our understanding of this disease through a local registry or other data collection efforts.”
With regard to the area involving the most potential controversy, that of the administration of hydroxychloroquine, with or without azithromycin, the IDSA panel writes, “The guideline panel recommends that, because of uncertainty regarding its risks and benefits, the use of HCQ should be in the context of a clinical trial. Because of the potential for toxicity, the panel recommends that the HCQ+AZ combination only be used in the context of a clinical trial. This recommendation does not address the use of azithromycin for secondary bacterial pneumonia in patients with COVID-19. Additional randomized controlled trials and prospective outcome registries are needed to inform research for treatment with HCQ alone or in combination with azithromycin for patients with COVID-19 (Table s2. Best practices/suggestions for research of treatments for patients with COVID-19).”
