FRAGILE-COLCOVID19: A Clinical Trial Based on Early Administration of an Oral Combination of Colchicine and Prednisone in Elderly Patients with COVID-19 in Geriatric Facilities

Abstract

Background: Unprotected and fragile elderly people in nursing homes experienced the highest mortality rates during the initial coronavirus disease 2019 (COVID-19) pandemic.

Objective: Our aim was to study the role of two oral anti-inflammatory drugs, colchicine and prednisone, in elderly patients with COVID-19 in geriatric centers.

Methods: A phase II/III, randomized, controlled, multicenter clinical trial was performed in a geriatric population comparing the efficacy and safety of an oral combination of prednisone (60 mg/day for 3 days) and colchicine (at loading doses of 1-1.5 mg/day for 3 days, followed by 0.5 mg/day for 11 days) with the standard treatment, based on intravenous dexamethasone. Primary endpoints assessed the efficacy in reducing death or the modified endpoint death/therapeutic failure to the study drugs over a 28-day period, while secondary endpoints included safety, laboratory changes, and additional therapies used.

Results: Fifty-four patients (35 female/19 male) were enrolled, 25 (46.3%) of whom were allocated to the experimental arm and 29 (53.7%) to the control arm. At day 28, no differences in deaths were observed. The combination of mortality or therapeutic failure occurred in 12 (45.13%) patients receiving dexamethasone and 6 (28.13%) patients receiving colchicine/prednisone, resulting in a reduction of risk difference (RD) of - 17% (p = 0.17), with an average reduction of 39% (risk ratio [RR] 0.61) in patients receiving colchicine/prednisone (p = 0.25). Control patients received higher amounts of additional glucocorticoids (p = 0.0095) over a longer time frame (p = 0.0003). Colchicine/prednisone significantly reduced ferritin levels at day 14, as well as D-dimer and lactate dehydrogenase (LDH) levels at day 28. Adverse events were similar in both groups.

Conclusions: The combination colchicine/prednisone compared with intravenous dexamethasone has shown a remarkable trend to increase disease survival over a 28-day period in elderly patients requiring oxygen therapy in geriatric centers, without safety issues.

Clinical trial registry: Clinical Trials Registration Number: NCT04492358.

Fig. 1

Study flow diagram. ^aPatients excluded from the per-protocol population: one patient was taking prednisone 5 mg/day before enrollment in the study (met an exclusion criteria), and one patient stopped taking the study medications at day 3 for a decision from the patient’s treating physician. In the ITT/safety population, 42 (77.8%) patients completed the study [23 (79.3%) and 19 (76%) cases in the control and experimental groups, respectively]. Thirty-five (66%) patients completed the study according to the protocol [17 (73.9%) in the control group and 18 (94.7%) in the experimental group]. ITT intention-to-treat, PP per-protocol