Cochrane COVID-19 Study Register
Study record
RBR-8jyhxhFirst Published: 2020 Aug 24Updated Date: 2021 Mar 1

Clinical trial for the treatment of COVID-19 with Chloroquine and Colchicine

  1. Study Type
  2. Interventional
  1. Study Aim
  2. Treatment and Management
  1. Study Design
  2. Parallel/Crossover
  1. Intervention Assignment
  2. Randomised
  1. Population (8)
  2. Male and Female
  3. Severe COVID-19
  4. Moderate COVID-19
  5. Adult
  6. Aged (65+)
  1. Intervention (1)
  2. Colchicine
  1. Comparison (1)
  2. Placebo
  1. Outcome (5)
  2. Death
  3. Oxygen Therapy
  4. Admission to Intensive Care Unit
  5. Time-to-Event
  6. Duration Of Hospital Stay
Reference record

Clinical trial for the treatment of COVID-19 with Chloroquine and Colchicine

Hospital das Clinicas de Ribeirao Preto - Ribeirao Preto, SP, Brazil
Trial registry record
No Results
INTERVENTION: Drug Drug Therapy Randomized clinical trial for treatment of COVID-19 with chloroquine and placebo versus chloroquine and colchicine. Intervention chloroquine - hydroxychloroquine sulfate 400 mg bid for 1 or 2 (if body weight greater than 80 kg) days, followed by 400 mg daily until 10 days of treatment. Intervention colchicine - colchicine 0,5 mg tid for 5 days, followed by 0,5 mg bid for 5 days. If body weight greater than 80 kg, a loading dose of 1 mg will be used. Chloroquine and placebo experimental group: 30 subjects with moderate or severe forms of COVID-19 will receive the intervention chloroquine and placebo according to the scheme: 1 tablet every 8 hours for 5 days, followed by 1 tablet every 12 hours for 5 days. Experimental group chloroquine and colchicine: 30 subjects with moderate or severe forms of COVID-19 will receive the interventions chloroquine and colchicine. CONDITION: B34.2 B34.2 - Coronavirus infection, unspecified Coronavirus disease 2019 (COVID-19) ; B34.2 - Coronavirus infection, unspecified PRIMARY OUTCOME: To evaluate the duration of oxygen therapy for both groups, measured in number of days of need of supplemental oxygen by catheter or masks.; To evaluate the hospitalization time for both groups, measured in number of days from the admission to the discharge. To evaluate the percentage of death. To evaluate the percentage of individuals who will require admission to the Intensive Care Unit, due to clinical deterioration. In this situation, due to institutional restriction, the study drugs will be discontinued. SECONDARY OUTCOME: Assess the percentage of individuals who will experience adverse events of any kind. Assess the percentage of treatment interruption due to adverse event. INCLUSION CRITERIA: Moderate or severe forms of COVID-19; 18 years or older; body weight of 50 kg or more; serum Ca2+ and K+ normal; QT interval lower than 450 ms at 12 derivations electrocardiogram; beta-HCG (serum or urine) negative (if woman under 50)
Reference record

Beneficial effects of colchicine for moderate to severe COVID-19: an interim analysis of a randomized, double-blinded, placebo controlled clinical trial (preprint)

Lopes MIF, Bonjorno LP, Giannini MC, Amaral NB, Benatti MN, Rezek UC, Emrich-Filho LL, Sousa BAA, Almeida SCL, Luppino-Assad R, Veras FP, Schneider A, Rodrigues TS, Leiria LOS, Cunha LD, Alves-Filho JC, Cunha TM, Neto EA, Miranda CH, Pazin-Filho A, Martins MA, Borges MC, Fonseca BAL, Bollela VR, Cunha FQ, Zamboni DS, Santana RC, Vilar FC, Louzada-Junior P, Oliveira RDR
Unpublished article (preprint)
Report Results
Introduction. Neutrophilia and high levels of proinflammatory cytokines and other mediators of inflammation are common finds in patients with severe acute respiratory syndrome due to COVID-19. By its action on leukocytes, we propose colchicine as an intervention worthy of being tested. Objective. To evaluate whether the addition of colchicine to standard treatment for COVID-19 results in better outcomes. Methods. We present the interim analysis of a single-center randomized, double-blinded, placebo controlled clinical trial of colchicine for the treatment of moderate to severe COVID-19, with 38 patients allocated 1:1 from April 11 to July 06, 2020. Colchicine regimen was 0.5 mg thrice daily for 5 days, then 0.5 mg twice daily for 5 days. The first dose was 1.0 mg whether body weight was ≥ 80 kg. Endpoints. The primary endpoints were the need for supplemental oxygen; time of hospitalization; need for admission and length of stay in intensive care units; and death rate and causes of mortality. As secondary endpoints, we assessed: serum C-reactive protein, serum Lactate dehydrogenase and relation neutrophil to lymphocyte of peripheral blood samples from day zero to day 7; the number, type, and severity of adverse events; frequency of interruption of the study protocol due to adverse events; and frequency of QT interval above 450 ms. Results. Thirty-five patients (18 for Placebo and 17 for Colchicine) completed the study. Both groups were comparable in terms of demographic, clinical and laboratory data at baseline. Median (and interquartile range) time of need for supplemental oxygen was 3.0 (1.5-6.5) days for the Colchicine group and 7.0 (3.0-8.5) days for Placebo group (p = 0.02). Median (IQR) time of hospitalization was 6.0 (4.0-8.5) days for the Colchicine group and 8.5 (5.5-11.0) days for Placebo group (p = 0.03). At day 2, 53% vs 83% of patients maintained the need for supplemental oxygen, while at day 7 the values were 6% vs 39%, in the Colchicine and Placebo groups, respectively (log rank; p = 0.01). Hospitalization was maintained for 53% vs 78% of patients at day 5 and 6% vs 17% at day 10, for the Colchicine and Placebo groups, respectively (log rank; p = 0.01). One patient per group needed admission to ICU. No recruited patient died. At day 4, patients of Colchicine group presented significant reduction of serum C-reactive protein compared to baseline (p < 0.001). The majority of adverse events were mild and did not lead to patient withdrawal. Diarrhea was more frequent in the Colchicine group (p = 0.17). Cardiac adverse events were absent. Discussion. The use of colchicine reduced the length of supplemental oxygen therapy and the length of hospitalization. Clinical improvement was in parallel with a reduction on serum levels of C-reactive protein. The drug was safe and well tolerated. Colchicine may be considered a beneficial and not expensive option for COVID-19 treatment. Clinical trials with larger numbers of patients should be conducted to further evaluate the efficacy and safety of colchicine as an adjunctive therapy for hospitalized patients with moderate to severe COVID-19.Competing Interest StatementThe authors have declared no competing interest.Clinical TrialRBR-8jyhxhClinical Protocolshttp://www.ensaiosclinicos.gov.br/rg/RBR-8jyhxh/Funding StatementFAPESP grants (2013/08216-2, 2020/05601-6), CNPq (425075/2016-8) and CAPES grants.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The trial is registered on the National Registry under the alphanumeric code RBR-8jyhxh (http://www.ensaiosclinicos.gov.br/rg/RBR-8jyhxh/) and it was approved by National Ethics Committee (CONEP; CAAE: 30248420.9.3001.5403).All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any othe prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesI declare that all clinical and laboratory data presented in the manuscript are promptly available. [Preprints are preliminary reports of work that have not been peer reviewed. Refer to the original preprint or preprint server for specific information about the individual preprint.]
Reference record

Beneficial effects of colchicine for moderate to severe COVID-19: a randomised, double-blinded, placebo-controlled clinical trial

Lopes MI, Bonjorno LP, Giannini MC, Amaral NB, Menezes PI, Dib SM, Gigante SL, Benatti MN, Rezek UC, Emrich-Filho LL, Sousa BAA, Almeida SCL, Luppino Assad R, Veras FP, Schneider A, Rodrigues TS, Leiria LOS, Cunha LD, Alves-Filho JC, Cunha TM, Arruda E, Miranda CH, Pazin-Filho A, Auxiliadora-Martins M, Borges MC, Fonseca BAL, Bollela VR, Del-Ben CM, Cunha FQ, Zamboni DS, Santana RC, Vilar FC, Louzada-Junior P, Oliveira RDR
Journal article
Report Results
OBJECTIVE: To evaluate whether the addition of colchicine to standard treatment for COVID-19 results in better outcomes. DESIGN: We present the results of a randomised, double-blinded, placebo-controlled clinical trial of colchicine for the treatment of moderate to severe COVID-19, with 75 patients allocated 1:1 from 11 April to 30 August 2020. Colchicine regimen was 0.5 mg thrice daily for 5 days, then 0.5 mg twice daily for 5 days. The primary endpoints were the need for supplemental oxygen, time of hospitalisation, need for admission and length of stay in intensive care unit and death rate. RESULTS: Seventy-two patients (36 for placebo and 36 for colchicine) completed the study. Median (and IQR) time of need for supplemental oxygen was 4.0 (2.0-6.0) days for the colchicine group and 6.5 (4.0-9.0) days for the placebo group (p<0.001). Median (IQR) time of hospitalisation was 7.0 (5.0-9.0) days for the colchicine group and 9.0 (7.0-12.0) days for the placebo group (p=0.003). At day 2, 67% versus 86% of patients maintained the need for supplemental oxygen, while at day 7, the values were 9% versus 42%, in the colchicine and the placebo groups, respectively (log rank; p=0.001). Two patients died, both in placebo group. Diarrhoea was more frequent in the colchicine group (p=0.26). CONCLUSION: Colchicine reduced the length of both, supplemental oxygen therapy and hospitalisation. The drug was safe and well tolerated. Once death was an uncommon event, it is not possible to ensure that colchicine reduced mortality of COVID-19. TRIAL REGISTRATION NUMBER: RBR-8jyhxh