Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019

Abstract

IMPORTANCE Severe acute respiratory syndrome coronavirus 2 infection has evolved into a global pandemic. Low-dose colchicine combines anti-inflammatory action with a favorable safety profile. OBJECTIVE To evaluate the effect of treatment with colchicine on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019 (COVID-19). DESIGN, SETTING, AND PARTICIPANTS In this prospective, open-label, randomized clinical trial (the Greek Study in the Effects of Colchicine in COVID-19 Complications Prevention), 105 patients hospitalized with COVID-19 were randomized in a 1:1 allocation from April 3 to April 27, 2020, to either standard medical treatment or colchicine with standard medical treatment. The study took place in 16 tertiary hospitals in Greece. INTERVENTION Colchicine administration (1.5-mg loading dose followed by 0.5 mg after 60 min and maintenance doses of 0.5 mg twice daily) with standard medical treatment for as long as 3 weeks. MAIN OUTCOMES AND MEASURES Primary end points were (1) maximum high-sensitivity cardiac troponin level; (2) time for C-reactive protein to reach more than 3 times the upper reference limit; and (3) time to deterioration by 2 points on a 7-grade clinical status scale, ranging from able to resume normal activities to death. Secondary end points were (1) the percentage of participants requiring mechanical ventilation, (2) all-cause mortality, and (3) number, type, severity, and seriousness of adverse events. The primary efficacy analysis was performed on an intentionto-treat basis. RESULTS A total of 105 patients were evaluated (61 [58.1%] men; median [interquartile range] age, 64 [54-76] years) with 50 (47.6%) randomized to the control group and 55 (52.4%) to the colchicine group. Median (interquartile range) peak high-sensitivity cardiac troponin values were 0.0112 (0.0043-0.0093) ng/mL in the control group and 0.008 (0.004-0.0135) ng/mL in the colchicine group (P = .34). Median (interquartile range) maximum C-reactive protein levels were 4.5 (1.4-8.9) mg/dL vs 3.1 (0.8-9.8) mg/dL (P = .73), respectively. The clinical primary end point rate was 14.0% in (continued) Key Points Question Is the receipt of colchicine among patients hospitalized with symptomatic coronavirus disease 2019 associated with clinical benefit? Findings In this randomized clinical trial of 105 patients, the rate of the primary clinical end point (clinical deterioration) was higher in the control group than in the colchicine group, and the time to clinical deterioration was shorter in the control group than in the colchicine arm. No difference was observed in the primary biochemical end point (highsensitivity troponin concentration), but patients in the colchicine group had a smaller increase in dimerized plasma fragment D compared with patients in the control group. Meaning The hypothesis-generating findings of this study suggest a role for colchicine in the treatment of patients with coronavirus disease 2019.

Interventions for treatment of COVID-19: A living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)

“…Two trials compared convalescent plasma added to standard care versus standard care alone [ 40 , 52 ]. The remaining trials and comparisons included hydroxychloroquine with and without azithromycin added to standard care versus standard care alone [ 55 ], hydroxychloroquine versus placebo [ 54 , 68 ], hydroxychloroquine and chloroquine added to standard care versus standard care alone [ 49 ], methylprednisolone added to standard care versus standard care alone [ 57 ], lopinavir–ritonavir versus umifenovir and versus standard care [ 41 ], favipravir versus umifenovir [ 34 ], high-flow nasal oxygenation versus standard mask oxygenation prior to fibreotic tracheal intubation [ 45 ], α-lipoic acid versus placebo [ 47 ], the combination of novaferon plus lopinavir–ritonavir versus novaferon and versus lopinavir–ritonavir [ 46 ], baloxavir marboxil versus favipiravir and versus standard care [ 42 ], 5 versus 10 days of remdesivir [ 38 ], interferon β-1a added to standard care versus standard care alone [ 37 ], colchicine added to standard care versus standard care alone [ 50 ], high-dosage with low-dosage chloroquine diphosphate [ 51 ], intravenous immunoglobulin added to standard care versus standard care alone [ 58 ], ribavirin plus interferon alpha versus lopinavir/ritonavir plus interferon alpha versis ribavirin plus lopinavir/ritonavir plus interferon alpha [ 62 ], darunavir/cobicistat plus interferon alpha-2b versus interferon alpha-2b alone [ 61 ], lincomycin HCl versus azitromycin [ 63 ], 99mTc-methyl diphosphonate (99mTc-MDP) injection added to standard care versus standard care alone [ 64 ], and interferon alpha-2b plus gamma versus interferon alpha-2b alone [ 65 ].…”

“…One single trial randomizing 81 participants compared high-dosage versus low-dosage chloroquine diphosphate showed evidence of a beneficial effect of low-dosage chloroquine on all-cause mortality ( p = 0.024) [ 51 ]. One single trial randomizing 110 participants compared colchicine added to standard care versus standard care alone showed evidence of a beneficial effect of standard care on adverse events not considered serious ( p = 0.003) [ 50 ]. One single 3 group trial randomizing 667 participants to hydroxychloroquine with or without azithromycin versus standard care showed evidence of a harmful effect of hydroxychloroquine with azithromycin on adverse events not considered serious ( p = 0.015) [ 55 ].…”

“…The first is a network meta-analysis just published in BMJ [ 77 ]. However, at the time of publication, this project did not include all relevant trials [ 50 , 52 , 54 – 56 , 59 – 61 , 64 ], including the pivotal trials assessing the effects of hydroxychloroquine [ 54 , 55 , 59 ].…”

Efficacy of various treatment modalities for nCOV‐2019: A systematic review and meta‐analysis

“…Eighteen studies were from China, 10,11,[31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] six from USA, [47][48][49][50][51][52] five from Italy, [53][54][55][56][57] two from France 6,58 and one each from Brazil, 59 Hong Kong, 60 Spain 61 and Greece. 62 There was no significant difference in the mean age and sex distribution between any of the treatment and comparator groups included in our meta-analysis. Table 2 depicts the baseline characteristics of clinical studies included in the systematic review and meta-analysis.…”

The Impact of Colchicine on The COVID-19 Patients; A Clinical Trial Study

“…In Spyridon et al study (18), about the colchicine effect on cardiac and in ammatory biomarkers in COVID-19 admitted patients. Mean (SD) event-free survival time was 18.6 (0.83) days the in the control group vs 20.7 (0.31) in the colchicine group (log rank P = 0.03).…”