Colchicine for Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement

NCT04870424 | Completed Phase 3 DMC

• 1 other identifier: Co-STAR
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Transcatheter aortic valve implantation (TAVI) is a well-established alternative to surgical aortic valve replacement for the treatment of patients with symptomatic severe aortic stenosis. While peri-procedural complications such as stroke, vascular complications and bleeding have substantially declined with the refinement of transcatheter valves and increasing experience, new-onset atrial fibrillation (NOAF) or atrioventricular conduction disturbances continue to occur in almost half of all patients. Colchicine is a well-known substance that has been approved for the treatment of acute gout flares and familial Mediterranean fever in many countries. Colchicine has proven safe and effective in the prevention of atrial fibrillation after cardiac surgery. The anti-inflammatory effects of colchicine may mitigate the occurrence of atrioventricular conduction disturbances and thus the need for the implantation of a permanent pacemaker post transcatheter aortic valve implantation. The objective of the Co-STAR-Trial is to investigate the efficacy of colchicine for the prevention of new-onset atrial fibrillation and conduction disturbances requiring the implantation of a permanent pacemaker in patients undergoing transcatheter aortic valve implantation. Co-STAR is an investigator-initiated, randomized, double blind, placebo-controlled trial. A total of 200 patients referred for treatment of symptomatic severe aortic stenosis and selected to undergo TAVI will be randomized in a 1:1 ratio to the treatment with Colchicine or placebo for 30 days post transcatheter aortic valve implantation.

Conditions

Transcatheter Aortic Valve Replacement; Atrial Fibrillation New Onset; Pacemaker; Colchicine

Outcome Measures

Primary Outcomes (1)

• Incidence rate of the composite of new onset atrial fibrillation or occurrence of conduction disturbances requiring the implantation of a permanent pacemaker

  Assessed based on extended rhythm monitoring performed until 7 days post-discharge as well as clinically or incidentally captured episodes of NOAF captured during routine care thereafter. NOAF is defined as at least one episode of atrial fibrillation with a duration \>30s.

  30 days

Secondary Outcomes (8)

• Single components of primary composite endpoint

  30 days and 1 year

• The incidence of conductance disturbances

  30 days, 1 year

• The predictors of conductance disturbances

  30 days, 1 year

• The incidence of new arrhythmias resulting in hemodynamic instability or requiring therapy

  30 days, 1 year

• Inflammatory marker levels

  at day 1

Other Outcomes (1)

• Safety Outcome

  30 days

Study Arms (2)

Colchicine

EXPERIMENTAL

Drug: Colchicine

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Colchicine DRUG

Colchicine in a loading dosage of 1mg single dose per os the day before TAVI and 1mg single dose at the day of procedure. Thereafter, colchicine 0.5mg once daily per os up to post-procedural day 12.

Colchicine

Placebo DRUG

Placebo once daily per os the day before TAVI and once at the day of procedure. Thereafter, once daily per os up to post-procedural day 12.

Placebo

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Age ≥ 65 years
• Symptomatic severe aortic stenosis defined by an aortic valve area (AVA) ≤1.0 cm2 or an AVA indexed to body surface area \<0.6cm2/m2
• Selected to undergo transfemoral TAVI based on heart team decision

You may not qualify if:

• Life expectancy \<1 year irrespective of valvular heart disease
• Kidney disease with a creatinine clearance ≤30 ml/min
• Known severe liver disease
• Known neuromuscular disease
• Clinically significant anaemia with haemoglobin \<80g/L
• Known inflammatory bowel disease or chronic diarrhea
• Known ongoing bacterial infection
• Known galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
• Current treatment with colchicine, steroids or biologicals for any indication
• Concomitant intake of Cyclosporine, Amiodarone, Clarithromycin, Erythromycin, Omeprazole, Verapamil or other strong inhibitors of CYP3A4 or P-Glycoprotein
• Concomitant intake of Carbamazepin, Phenobarbital, Phenytoin, Rifampicin or other strong inductors of CYP3A4 and P-Glycoprotein
• Permanent pacemaker or implantable cardioverter defibrillator
• History of atrial fibrillation
• Absence of sinus rhythm on hospital admission
• Planned non-cardiac surgery within 30 days

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

Inselspital, Bern University Hospital, Department of Cardiology

Bern, 3010, Switzerland

Location

Related Publications (1)

• Ryffel C, Lanz J, Guntli N, Samim D, Furholz M, Stortecky S, Tomii D, Heg D, Boscolo Berto M, Peters AA, Reineke D, Reichlin T, Grani C, Windecker S, Pilgrim T. Colchicine in patients with aortic stenosis undergoing transcatheter aortic valve replacement: a double-blind randomized trial. Nat Commun. 2025 Jul 15;16(1):6501. doi: 10.1038/s41467-025-61916-6.

  PMID: 40659682 DERIVED

MeSH Terms

Interventions

Colchicine

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Officials

• Thomas Pilgrim, Prof.

  University of Bern, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2021
• First Posted: May 3, 2021
• Study Start: September 21, 2021
• Primary Completion: May 26, 2024
• Study Completion: June 3, 2025
• Last Updated: June 22, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)