Can Colchicine and Kaletra Cure COVID-19?

^{By Douglas L. Jennings, PharmD, FACC, FAHA, FCCP, FHFSA, BCPS}

The heat of summer swells as COVID-19 cases surge across most of the United States. Unfortunately rates of hospitalization and death are now also rising, as effective treatment options remain largely elusive. As discussed in prior blogs of mine, remdesivir and dexamethasone have demonstrated therapeutic potential for COVID-19, while other drugs like hydroxychloroquine seems largely ineffective.

The Greek Study in the Effects of Colchicine in COVID-19 Complications Prevention (GRECCO) randomized 105 patients with laboratory-confirmed SARS-CoV-2 infection and at least two clinical symptoms from 16 hospitals in Greece to receive either colchicine or standard medical treatment for up to 3 weeks. The primary endpoint was time to deterioration (defined as 2 points on a 7-grade clinical status scale, ranging from resuming normal activities to death). Clinical deterioration occurred in one patient in the colchicine group versus seven in the control group (OR 0.11, 95% CI 0.01-0.96, P=0.046) without no noted difference in C-reactive protein or troponin levels. While these preliminary findings are encouraging, this trial is very small, and it enrolled patients in April before new agents like remdesivir were available. As such confirmation in a larger contemporary cohort is required before colchicine can be recommended.

Meanwhile, the WHO announced earlier this month that they will discontinue the use of lopinavir/ritonavir for COVID-19 after interim trial results showed that this agent produced little or no reduction in the mortality of hospitalized patients when compared to standard of care. In addition, French researchers reported in paper published last week reported a possible risk of significant bradycardia with lopinavir/ritonavir. These authors found that the heart rate dropped below 60 bpm for more than 24 hours in nine out of 41 COVID-19 patients in the ICU who were on lopinavir/ritonavir during the first month of the outbreak. Furthermore, of those nine patients, eight experienced sinus bradycardia and one had third degree atrioventricular block. Taken together, this agent should not be used specifically to treat COVID-19 infection.

As the fight against COVID-19 rages on, the search for new therapies continues. Lopinavir/ritonavir seems to hold little promise as of now, at least as monotherapy (some limited data suggest efficacy when combined with other antivirals). Colchicine now some limited literature to suggest a benefit, but additional study is needed before this agent can be widely recommended, especially in light of the known side effects for this drug.

Dr Jennings is currently an Associate Professor of Pharmacy at Long Island University and the clinical pharmacist for the Heart Transplant and LVAD teams at NewYork- Presbyterian Hospital Columbia University Irving Medical Center.  He is an active researcher in his field, and he has published over 120 peer-reviewed abstracts and manuscripts, primarily focusing on the pharmacotherapy of patients under mechanical circulatory support. As a recognized expert in this area, he has been invited to speak at numerous national and international venues, including meetings in France, Saudia Arabia, India. Finally, Dr. Jennings has been active in professional organizations throughout his career. He is a fellow of the American College of Clinical Pharmacy, the American College of Cardiology, the Heart Failure Society of America, and the American Heart Association. 

References:

1. Deftereos SG, Giannopoulos G, Vrachatis DA, et al. Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial. JAMA Netw Open. 2020;3(6):e2013136. Published 2020 Jun 1. doi:10.1001/jamanetworkopen.2020.13136
2. World Health Organization. WHO discontinues hydroxychloroquine and lopinavir/ritonavir treatment arms for COVID-19 [press release]. https://www.who.int/news-room/detail/04-07-2020-who-discontinues-hydroxychloroquine-and-lopinavir-ritonavir-treatment-arms-for-covid-19. July 4, 2020.
3. Beyls C, Martin N, Hermida A, Abou-Arab O, Mahjoub Y. Lopinavir-ritonavir Treatment for COVID-19 Infection in Intensive Care Unit: Risk of Bradycardia [published online July 9, 2020]. Circulation. doi: https://doi.org/10.1161/CIRCEP.120.008798