Recently, a Japanese and Bangladeshi-led research team completed a retrospective study involving 325 consecutive patients infected with SARS-CoV-2 at the COVID-19 treatment unit at Mymensingh Medical College hospital (MMCH), Mymensingh, Bangladesh from April to June 2020. The study’s results were published online Sept. 24 in peer-reviewed Archivos de Bronconeumologia. With a total of 248 adult patients infected with SARS-CoV2 free of any pathological conditions, 115 of them received ivermectin plus standard of care while 133 of the subjects only received standard of care. The remaining patients, 77 in total who were under 18, were transferred from other facilities and received different care management approaches. The study team compared both arms of this study including ivermectin (N=115) and standard of care (N=133) in terms of 1) time to SARS-CoV-2 negativity, 2) disease progression (e.g. condition worsens from pneumonia to severe respiratory distress), 3) duration of hospital stay, and 4) mortality rate. The ivermectin treatment produced no aberrant symptoms (e.g. adverse safety events). While none of the ivermectin patients showed progressive pathology (e.g. pneumonia or cardiovascular complications), 9.8% of the standard of care group developed pneumonia and 1.5% had ischemic stroke. While only 9.6% of the ivermectin group ultimately required oxygen inhalation, 45.9% of the standard of care group fell in this category—a marked and material difference. This observation held up for the development of respiratory distress as well (2.6% ivermectin vs. 15.8% standard of care group). Moreover, of those patients needing antibiotic treatment, superiority of ivermectin was clear with 15.7% of the ivermectin groups vs. 60.2% of the standard of care group. Patients that were given ivermectin didn’t end up in the ICU nearly as much (0.9% ivermectin vs. 8.3% standard of care). Finally, those patients in the ivermectin arm got better faster. In a striking observation, those administered ivermectin became COVID-19 negative in a median of 4 days vs. 15 days for the standard of care group, at 95% CL, 8.97-10.59,P. Although the researchers acknowledge randomized, multicenter study could strengthen the evidence, they’re clear that ivermectin should be considered as a first-line therapy as part of a COVID-19 containment strategy.
Study Suggests Action in the West
Recently published by Elsevier, this study “Ivermectin Treatment May Improve the Prognosis of Patients with COVID-19,” authored by Khan MSI, Debnath CR, Nath PN, Mahtab MA, Nabeka H, Matsuda S, and Akbar SMF, produced materially provocative data indicating that Western research agencies and non-government organizations seeking economical, efficient and available treatments for SARS-CoV-2 should at least commission studies to further investigate and validate the accumulating real world evidence.
FDA Embraces Real World
A retrospective study, critics can undoubtedly point to the fact that this particular study wasn’t designed as a randomized controlled trial. However, the U.S. Food and Drug Administration (FDA) established guidance around Real World Data (RWD) and Real World Evidence (RWE) for a reason. In fact, with the passage in the U.S. of the 21st Century Cures Act back in 2016 the additional focus on the use of observational data, retrospective study data and more was acknowledged and recognized as important contributors to support regulatory decision making, including approvals for new indications for approved drugs.
Moreover, TrialSite has been accumulating volumes of case series, observational studies and the results from a couple randomized controlled trials suggesting the importance of ivermectin-based inquiry in association with COVID-19.
A Multi-faceted Strategy to Contain COVID-19
The authors convey that not only does the antiparasitic drug evidence expedite clearance of the novel coronavirus as observed in this retrospective study, but also represents a possible candidate therapy to manage the course of disease.
After all, the authors remind all, COVID-19 won’t go away. Rather, the world now experiences a marked rise in cases, especially in low and middle-income countries (LMICs) in select parts of Asia and Latin America. The authors suggest a flexible containment and patient management strategy, depending on country, economics, etc. TrialSite concurs within this point of view; these findings, which although not derived from randomized controlled studies, nonetheless represent an accumulating mountain of evidence that this drug can actually be part of a containment strategy for at least LMICs.
The authors although recognizing the importance of an additional multicenter randomized controlled study to strengthen the evidence, regardless suggests that based on the findings of this retrospective study, health authorities should consider ivermectin as a first-line therapy for containing COVID-19 to prevent disease progression and as part of a strategy to help reduce community transmission.
The Trial Site
A government medical school in Bangladesh, Mymensingh Medical College was established in 1924 by Earl of Lytton, then the governor of Bengal as The Lytton Medical School during British colonial times. Mymensingh Medical Journal, Index Medicus/MEDLINE listed, is the official journal of Mymensingh Medical College.
The postgraduate government medical college conducting MBBS, BDS and postgraduate courses across 27 disciplines is affiliated with Dhaka University and Bangabandhu Sheikh Medical University (BSMMU). More on the hospital can be read here.
· Saiful Islam Khan, MD, Mymensingh Medical College and Hospital, COVID-19 Management Team
· Sakirul Islam Khan, PhD, Ehime University Graduate School of Medicine, Dept. of Anatomy & Embryology
· Chitto Ranjan Debnath, Mymensingh Medical College and Hospital, Dept. of Hepatology
· Progga Nanda Nath, Mymensingh Medical College and Hospital, COVID-19 Management Team
· Mamun AlMahtab, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
· Hiroaki Nebeka, Ehime University Graduate School of Medicine, Dept. of Anatomy & Embryology
· Seiji Matsuda Sheikh, Ehime University Graduate School of Medicine, Dept. of Anatomy & Embryology
· Mohammad Fazle Akbar, Ehime University Graduate School of Medicine, Dept. of Gastroenterology
Call to Action: The study team suggests a multicenter, double-blind, drug-controlled study to strengthen the evidence. TrialSite has sent an email to NIH Director Francis Collins, recommending that the mighty research agency fund an ivermectin clinical trial, notably suggesting the effort currently underway involving Dr. Jean-Jacques Rajter and the follow-up to his ICON study in Broward County, Florida.