Study to Investigate the Treatment Effect of Colchicine in Patients With COVID-19

COVID-19 Clinical Trial

Official title:

Study to Investigate the Treatment Effect of Colchicine in Patients With COVID-19

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04667780
• Other study ID #: ATH/IRB/Colchicine/25.11.2020
• Status: Completed
• Phase: Phase 3
• Start date: December 1, 2020
• Est. completion date: July 9, 2021

Study information

• Verified date: January 2023
• Source: Ayub Teaching Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

COVID-19 is associated with a cytokine storm that leads to respiratory distress, multiorgan failure and elevated mortality. Oral Colchicine exhibits high anti-inflammatory capacity attributed to the inhibition of microtubules polymerization, inflammasome and production of IL-1β and IL-6, which could prevent the inflammatory storm in COVID-19 patients at risk. The investigators present a randomized, controlled, open-labeled, and pragmatic clinical trial to study the treatment effect of Colchicine in COVID-19 patients requiring hospitalization, but no intensive care yet. Colchicine will be started within the first 48 hours and continue for 14 days using a descending dose. The benefits will be studied in terms of clinical evolution (WHO 7-point scale) and IL-6 levels, as well as other clinical and biochemical secondary end-points. In the case of positive results, the clinical impact would be relevant given that this oral medication is affordable and widely accessible which would help to prevent the inflammatory complications associated with COVID-19.

Description:

This is a Phase III, prospective, pragmatic, randomized, controlled and open-label trial, comparing standard of care vs. standard of care plus COLCHICINE for 14 days, in patients hospitalized due to COVID-19 and confirmed infection by SARS-CoV-2, within the first 48 hours after the hospital admission. Patients meeting severity criteria will be excluded, defined as established limitation of therapeutic effort or need for invasive mechanical ventilation at the time of inclusion. The Colchicine treatment includes an initial dose of 1.5 mg (1 mg and 0.5 mg two hours after), followed by 0.5 mg every 12 hours during the next 7 days and 0.5 mg every 24 hours until the completion of 14 days of total treatment. In patients receiving ritonavir or lopinavir or with reduced renal clearance (<50 ml/min/1.37m2), weight <70 kg or age >75 years old, the dose will be adjusted to the half.

Patients meeting all the inclusion criteria and none of the exclusion ones (see below), after signing the informed consent, will be centrally randomized to "Colchicine" or "Control" group. Patients in both groups will receive the standard therapy for COVID-19 as per the hospital protocols. Randomization will be controlled by: age, sex, time from initiation of symptoms, cardiovascular disease, the 7 point WHO and levels of C-reactive protein, ferritin, D-dimer, IL-6 and lymphocyte levels.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: July 9, 2021
• Est. primary completion date: July 9, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. SARS-CoV-2 infection confirmed by PCR.

2. Admitted in the hospital in the previous 48 hours, with clinical status 3, 4 or 5 of WHO classification.

3. Age above 18 years old.

4. Informed written consent.

Exclusion Criteria:

1. Invasive mechanical ventilation needed.

2. Established limitation of the therapeutic effort

3. Inflammatory bowel disease (IBD: Chron Syndrome or Ulcerative colitis), chronic diarrhea or malabsorption.

4. Previous neuromuscular disease.

5. Other disease with an estimated vital prognosis under 1 year.

6. Severe renal insufficiency (glomerular filtration rate <30 mL/min/1.73m2)

7. Medical records of cirrhosis, active chronic hepatitis or severe hepatic disease defined by GOT or GPT levels three times above the normal upper limit.

8. Patients with previous colchicine treatment for other diseases (mainly chronic prescriptions for familial Mediterranean fever or gout). Clearance period will not be required for patients treated with colchicine who stopped the treatment before the randomization.

9. Patients with history of allergic reaction or significant sensitivity to colchicine.

10. Treatment with immunosuppressive agents, corticoids or interleukine-1 antagonists for 6 months before inclusion.

11. Pregnant or breastfeeding female, confirmed by a positive result in the human chorionic gonadotropin (hCG) test.

12. Fertile woman, or post-menopausal during less than one year and non-surgically sterilized. Women of fertile age may be included if using at least one contraceptive method and preferably two complementary contraceptive methods.

13. Use of other investigational drugs in the moment of inclusion, or during 30 days previous to inclusion.

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Colchicine
Colchicine tablet 0.5 mg
• Standard COVID-19 care
As per the hospital guidelines

Locations

Country	Name	City	State
Pakistan	Ayub Teaching Hospital	Abbottabad	Khyber Pakhtunkhwa

Sponsors (2)

Lead Sponsor	Collaborator
Ayub Teaching Hospital	Universidad de Murcia

Country where clinical trial is conducted

Pakistan, 

References & Publications (2)

Deftereos SG, Giannopoulos G, Vrachatis DA, Siasos GD, Giotaki SG, Gargalianos P, Metallidis S, Sianos G, Baltagiannis S, Panagopoulos P, Dolianitis K, Randou E, Syrigos K, Kotanidou A, Koulouris NG, Milionis H, Sipsas N, Gogos C, Tsoukalas G, Olympios CD, Tsagalou E, Migdalis I, Gerakari S, Angelidis C, Alexopoulos D, Davlouros P, Hahalis G, Kanonidis I, Katritsis D, Kolettis T, Manolis AS, Michalis L, Naka KK, Pyrgakis VN, Toutouzas KP, Triposkiadis F, Tsioufis K, Vavouranakis E, Martinez-Dolz L, Reimers B, Stefanini GG, Cleman M, Goudevenos J, Tsiodras S, Tousoulis D, Iliodromitis E, Mehran R, Dangas G, Stefanadis C; GRECCO-19 investigators. Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial. JAMA Netw Open. 2020 Jun 1;3(6):e2013136. doi: 10.1001/jamanetworkopen.2020.13136. — View Citation

Scarsi M, Piantoni S, Colombo E, Airo P, Richini D, Miclini M, Bertasi V, Bianchi M, Bottone D, Civelli P, Cotelli MS, Damiolini E, Galbassini G, Gatta D, Ghirardelli ML, Magri R, Malamani P, Mendeni M, Molinari S, Morotti A, Salada L, Turla M, Vender A, Tincani A, Brucato A, Franceschini F, Furloni R, Andreoli L. Association between treatment with colchicine and improved survival in a single-centre cohort of adult hospitalised patients with COVID-19 pneumonia and acute respiratory distress syndrome. Ann Rheum Dis. 2020 Oct;79(10):1286-1289. doi: 10.1136/annrheumdis-2020-217712. Epub 2020 Jul 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in the patients' clinical status through the 7 points ordinal scale WHO R&D Blueprint expert group	Improvement in the clinical evolution of patients	up to 14 days
Primary	Changes in IL-6 concentrations	Improvement in cytokine level	up to 14 days
Secondary	Improvement in the clinical status	time needed to reduce at least 2 points in the 7-point Ordinal Scale for Clinical Improvement by WHO R&D Blueprint expert group (0-7)	up to 14 days
Secondary	Changes in the score for the Sequential Organ Failure Assessment (SOFA score)	Sequential Organ Failure Assessment (SOFA score) (0-14)	up to 14 days
Secondary	Changes in the punctuation in the National Early Warning Score	National Early Warning Score (NEWS scale)	up to 14 days
Secondary	Number of days with invasive mechanical ventilation		up to 14 days
Secondary	Number of days with high flow oxygen therapy		up to 14 days
Secondary	Changes in other inflammatory markers	C-reactive protein	up to 14 days
Secondary	Changes in severity markers	D-dimer	up to 14 days
Secondary	Changes in severity markers	Leukocytes	up to 14 days
Secondary	Changes in severity markers	Lymphocytes	up to 14 days
Secondary	Changes in severity markers	Platelets	up to 14 days
Secondary	Changes in severity markers	LDH	up to 14 days
Secondary	Changes in severity markers	Ferritin	up to 14 days
Secondary	Changes in myocardial damage	myocardial stress markers hsTnT	up to 14 days
Secondary	Changes in myocardial damage	myocardial stress markers NT-proBNP	up to 14 days
Secondary	Time until reaching a virus negative status	RT-PCR assay	up to 14 days
Secondary	Length of hospital stay	Length of hospital stay	up to 14 days
Secondary	Number of days in the intensive care unit.	Number of days in the intensive care unit.	up to 14 days
Secondary	Mortality	Mortality	up to 14 days