Impact of Colchicine in Hospitalized Colombian Patients With COVID-19

Study Overview
=================
Brief Summary
-----------------
This is a phase IIIa, prospective, open-label, randomized, parallel-group study designed to evaluate the efficacy and safety of oral colchicine plus standard therapy versus standard therapy in the clinical course of SARS-CoV-2 infection, in a population group with moderate COVID-19 compromise and requiring hospitalization.Aproximately 120 subjects meeting all inclusion and not inclusion criteria will be randomized to receive either Colchicine plus standard treatment or only standard treatment for 15 days

Detailed Description
-----------------
Introduction: COVID-19 and mortality associated with acute respiratory distress syndrome (ARDS) pose a global public health problem. The increase in spread and associated mortality poses a scenario where cost-effective therapeutic options are urgently and effectively proposed to control and reduce the pandemic and even to reduce the number of deaths Objective: To evaluate the efficacy and safety of oral colchicine plus treatment standard versus standard treatment in the clinical course of SARS-CoV-2 virus infection, in a population group with moderate COVID-19 involvement and requiring hospitalization. Methodology: A prospective, open, randomized, parallel-group study, the sample size of 120 subjects each arm of 60 subjects. Random assignment (1: 1) to either colchicine plus standard treatment or control arm (standard treatment) orally for 14 days. An initial dose of 1.5 mg orally on the first day, followed by 0.5 mg every 12 hours on days 2 to 7 and continuing with 0.5 mg a day until completing 14 days ± 1. It will be followed on days 1, 3, 7, 14, and day 28, evaluating physical examination, clinical situation, laboratories, and adverse events. The primary efficacy data correspond to the deterioration in the clinical status of the patients through the semiquantitative ordinal scale suggested by the WHO R&D committee. Expected results: It is expected to find out how, through different pathways, colchicine could act in modulating or preventing the appearance of ARDS associated with COVID-19, its possible effects on viral replication and antigenic presentation.

Official Title
-----------------
Impact of Colchicine in Hospitalized Colombian Patients With COVID-19

Conditions
-----------------
Corona Virus Infection

Intervention / Treatment
-----------------
* Drug: Colchicine 0.5 MG
* Combination Product: CONTROL GROUP


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients ≥18 years old. Laboratory-confirmed SARS-CoV-2 infection: infection confirmed with nasopharyngeal swab by positive RT PCR in the last 48 hours. Hospital admission for COVID-19 in the previous 48 hours. Clinical stage 3 (no supplemental oxygen requirement) or 4 (supplemental oxygen requirement for nasal contact lenses or mask) of the WHO classification (see ANNEX 2). The patient must be able and willing to provide informed written consent before performing study procedures. Patient confirmed to covid19 as positive by positive PCR test Exclusion Criteria: Pregnancy, nursing mothers, and women of childbearing potential who are unable to use adequate contraception. Known hypersensitivity or other clear contraindication to the use of colchicine. History of end-stage renal disease (eGFR <30 ml / min / 1.73 m2). Medical history of cirrhosis (Child-Pugh C), liver failure, chronic active hepatitis, or severe liver disease defined by alanine aminotransferase (ALT) or aspartate aminotransferase (AST)> 5 times the upper limit of normal. History of pre-existing neuromuscular disease. Previous severe hematologic disease or bleeding disorders. Inflammatory bowel disease (Crohn's disease or ulcerative colitis), chronic diarrhea, or malabsorptive syndrome. Colchicine treatment for other indications. Treatment with immunosuppressive/immunomodulatory agents, including glucocorticoids, antivirals, antimalarials, and IL 6 antagonists for 30 days prior to enrollment. Use of other investigational drugs at the time of inclusion, or during the 30 days prior to inclusion. Any medical condition or disease that, in the opinion of the investigator, may place the patient at unacceptable risk to participate in the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a phase IIIa, prospective, open-label, randomized, parallel-group study designed to evaluate the efficacy and safety of oral colchicine plus standard therapy versus standard therapy in the clinical course of SARS-CoV-2 infection, in a population group with moderate COVID-19 compromise and requiring hospitalization. Patients diagnosed with COVID-19 and meeting all eligibility criteria will be randomized for treatment in a 1: 1 ratio through a central voice response system. Randomization will be balanced in each of the 2 strata: 1) hospitalized patients with clinical stage 4 (requirement of supplemental oxygen by nasal contact lenses or mask) of the World Health Organization (WHO) classification, see ANNEX 2, who will receive in addition to the usual treatment for COVID-19 oral colchicine (exposed group); 2) hospitalized patients with clinical stage 4 of the WHO classification who will receive the usual treatment for COVID-19 (control group).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: COLHICINE PLUS STANDARD TREATMENT<br>Patients treated in the exposed group will consist of a decreasing dose of colchicine: a dose of 1.5 mg orally on the first day (initial 1 mg and 0.5 mg at 2 hours), followed by 0.5 mg every 12 hours on days 2 to 7, and continuing with 0.5 mg per day until completing 14 ± 1 days. The duration of treatment will be 14 ± 1 days, depending on the clinical judgment of the investigator. | Drug: Colchicine 0.5 MG<br>* Patientes in this arm will receive study medication colchicine 1,5 orally on the first day (initially two pills of 0,5 mg and 0.5 mg at 2 hours), followed by 0.5 mg every 12 hours on days 2 to 7, and continuing with 0.5 mg per day until completing 14 ± 1 days. The duration of treatment will be 14 ± 1 days, depending on the clinical judgment of the investigator.<br>* Other names: EXPOSED GROUP;|
| Placebo Comparator: STANDARD TREATMENT<br>In this case, the centers where the patients will be included adhere to the Colombian guidelines (Colombian Consensus of the Colombian Association of Infectious Diseases), and to standard treatment | Combination Product: CONTROL GROUP<br>* In this case, the centers where the patients are enrolled will adhere to the Colombian guidelines (Colombian Consensus of the Colombian Association of Infectious Diseases)<br>* Other names: standard treatment;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who die or require transfer to Intesive care unit | The primary endpoint will be the need of transfert to ICU or composite of dead due to COVID19 infection | In the first 15 days after ramdomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who die | The secondary end point is the ocurrence of death in the 15 days after ramdomization | 15 days after ramdomization | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Colchicine, Gout, Antirheumatic Agents, Tubulin Modulators