Trial NCT04326790
Publication Deftereos S, JAMA (2020) (published paper)
Dates: 03apr2020 to 27apr2020
Funding: Private (The study was funded by ELPEN Pharmaceuticals, Acarpia Pharmaceuticals, and Karian Pharmaceuticals.)
Conflict of interest: Yes

Methods
RCT
Blinding: Unblinded
Location : Multicenter / Greece
Follow-up duration (days): 21
Inclusion criteria
  • "1. Subjects >18 years old with laboratory confirmed SARS-COV-2 [by reverse transcription polymerase chain reaction (RT PCR)], who present with clinical symptoms including body temperature >37.5°C. AND 2. At least two of the following criteria: 6) persistent cough 7) persistent throat pain 8) anosmia, ageusia 9) asthenia 10) Arterial blood partial pressure of oxygen (PaO2)<95 mmHg."
Exclusion criteria
  • "1. Pregnancy, breastfeeding or unwillingness to take effective contraceptive measures during the clinical trial in women and men of childbearing potential. 2. Known hypersensitivity to colchicine or to any of the excipients of the product (lactose, gum arabic, sucrose, magnesium stearate, microcrystalline cellulose, polyvinylpyrrolidone, methylene casein, erythrosine lacquer). 3. Severe hepatic impairment. 4. Estimated glomerular filtration rate (eGFR) <20 ml/min/1.73m2. 5. Treating physician's clinical judgement that the patient will require mechanical respiratory support within 24 hours. 6. Any condition or circumstances which, at the discretion of the treating physician, would prevent the indicated follow-up of the participant. 7. Electrocardiographic QTc interval>450 msec. 8. Participation in a clinical trial with an investigational product (drug or medical device) or intervention. 9. Under treatment with colchicine for other indications. 10. A subject that, at the discretion of the Investigator, is unable to comply with the requirements of the clinical trial or his/her participation in it may put him/her at unacceptable risks for his/her health. 11. A subject undergoing haemodialysis. 12. Severe gastrointestinal failure, severe gastrointestinal disorders, or stomach ulcer. 13. Haematological disorders, such as blood diseases. 14. Under treatment or had received within the past 14 days drugs belonging to the classes of P-glycoprotein inhibitors or CYP3A4 enzyme inhibitors."
Interventions
Treatment
Colchicine
Initial dose: 1.5 mg orally followed by 0.5 mg an hour later if no adverse effect - Maintenance dose: 0.5 mg twice a day for a maximum of 21 days
Control
Standard care

Participants
Randomized
participants :
Colchicine=56
Standard care=54
Characteristics of participants
N= 110
Mean age : NR
61 males
Severity : Mild: n=0 / Moderate: n=102 / Severe: n=3 Critical: n=0
Number of vaccinated participants: NR
Primary outcome
In the register
Clinical deterioration in the semiquantitative ordinal scale suggested by the WHO R&D committee [ Time Frame: 3 weeks ] Time to clinical deterioration (2 levels in the WHO R&D Blueprint scale)
Maximal concentration of cardiac troponin [ Time Fr
In the report
The coprimary end points of the biochemical phase were the difference in maximal high-sensitivity cardiac troponin (hs cTn) levels between the 2 groups and the time for C-reactive protein to reach levels greater than 3 times the upper reference limit
Documents
available

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Yes
Risk of bias
Overall
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
Some concerns
General comment In addition to all available versions of the published article, the study registry, protocol, and statistical analysis plan were used in data extraction and risk of bias assessment. There is no change from the trial registration in the intervention and control treatments. Two types of primary outcomes were presented - a biochemical and a clinical. The biochemical primary outcome in the report partially reflects the primary outcome indicated in the registry.  Stated in the registry, it was "Maximal concentration of cardiac troponin [ Time Frame: 10 days ], Maximal concentration of high-sensitivity cardiac troponin" while in the report it was "the difference in maximal high-sensitivity cardiac troponin (hs cTn) levels between the 2 groups and the time for C-reactive protein to reach levels greater than 3 times the upper reference limit." The study did not reach its recruitment target of 180 patients as specified in the registry and protocol "because of slow enrollment as a result of the rapid flattening of the curve of COVID-19 cases in Greece."