Late Phase II study to evaluate the clinical benefit of the anti-inflammatory drug colchicine in patients with COVID-19

JRCT ID: jRCTs071220085

Registered date:06/01/2023

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Mild and moderate I COVID-19 patients in out-of-hospital care
• Date of first enrollment: 16/01/2023
• Target sample size: 100
• Study type: Interventional
• Intervention(s): Colchicine or placebo for 14 days each

Outcome(s)

• Primary Outcome: Number of fever-free days in 14 days

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(1) Patients with new-type coronavirus infection (COVID-19) with a fever of 37.5 degrees Celsius or higher on the day before assignment, confirmed by PCR or antigen, and who meet the following criteria
(1) Patients who fall under the Ministry of Health, Labour and Welfare (MHLW) Severity Classification*1 Mild or Moderate I (2,3,4 in the WHO ordinal scale for clinical improvement*2).
(2) One or more of the following symptoms are present
Runny or blocked nose, sore throat, shortness of breath, difficulty breathing, cough, lethargy, muscle or other aches, headache, chills
Feeling of fever, nausea, vomiting, diarrhea
(3) Patients whose disease onset and consent can be obtained within 5 days for hotel care patients and within 4 days for home care patients, and whose eligibility can be confirmed and allocation can be performed within the same period.
(4) Patients who are at least 18 years of age at the time consent is obtained
(5) In the case of women of childbearing potential or unprotected men*4, patients who agree to use adequate contraception from the time consent is obtained until 90 days after study drug administration
*1: Ministry of Health, Labour and Welfare Severity Classification
*2: WHO ordinal scale for clinical improvement
*3: Judgment is made based on medical history and medications. Obesity is judged based on self-reported weight and height.
*4: Sterilized men are defined as men who have been sterilized for at least one year after vasectomy and have documented absence of sperm at the time of ejaculation.
(6) Patients who can operate the following simple IT devices
The application is installed in the smart phone (not PC) and the data from the pulse oximeter is transmitted by Bluetooth function.
Can transmit automatically
Can use a smartphone for online medical services.
Receive and respond to web-based surveys, such as symptom surveys, via e-mail using a smartphone.
(7) Patients who have given a full explanation of their participation in this study, and who have given written consent of their own free will based on full understanding.

Exclude criteria

(1) Patients with a history of hypersensitivity to colchicine products
(2) Patients who are receiving colchicine or have taken colchicine in the 30 days prior to the date of eligibility testing
(3) Patients with cirrhosis of the liver
(4) Patients with clinically documented biliary stasis, or patients whose medical history indicates a concern for biliary stasis.
(5) Patients with concerns about impaired renal function at the time of eligibility testing (estimated from medical history and medications taken)
(6) Patients with active malignancy
(7) Patients taking drugs listed as "concomitant medications" in the colchicine package insert as drugs that may interact with colchicine, and patients taking or wishing to take Ensitrelvir Fumaric Acid (XOCOVA)
(1) Drugs that inhibit hepatic metabolizing enzyme CYP3A4, etc.
a. Drugs that strongly inhibit
Preparations containing atazanavir, clarithromycin, indinavir, itraconazole, nelfinavir, ritonavir (including nilmatrelvir/ritonavir tablets: paclovid pack), saquinavir, darunavir, telithromycin, telaprevir, cobicistat
b. moderately inhibiting drugs*.
Amprenavir, aprepitant, erythromycin, fluconazole, fosamprenavir
*However, because the maximum blood concentration of colchicine is approximately 1.3 times higher and the AUC is approximately 2 times higher when it is administered with verapamil, it is recommended that the study drug be administered as colchicine at a dose of 1.0 mg on the first day and 0.5 mg every other day from the following day to ensure that the maximum blood concentration of colchicine is 1.0 mg on the first day and 0.5 mg every other day from the following day. It is estimated that the pharmacokinetics will be similar to those without verapamil. Diltiazem has a 1.3-fold highest blood concentration and 1.2-fold highest AUC, so no dose adjustment is necessary7).
Drugs that inhibit P-glycoprotein
Cyclosporine
(8) Patients taking amiodarone or quinidine
(9) Patients taking diltiazem or verapamil whose doses will be increased during the study period
(10) Pregnant or possibly pregnant patients, lactating patients, and patients who wish to become pregnant during the study period (for female subjects of childbearing potential, eligibility will be determined at the subject interview and a pregnancy test will be performed with the test drug provided by the study before the first dose of medication).
(11) Patients who are currently participating in another clinical trial/clinical study or have participated in another clinical trial/clinical study within 30 days prior to obtaining consent
(12) Other patients who are deemed inappropriate for this study by the investigators.

Related Information

• Primary Sponsor: Kinjo Takeshi
• Secondary Sponsor: Ueda Shinichiro