Colchicine for Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement

Phase 3

Active, not recruiting

• Conditions: Atrial Fibrillation New Onset; Transcatheter Aortic Valve Replacement; Colchicine; Pacemaker
• Interventions: Drug: Placebo; Drug: Colchicine

• Registration Number: NCT04870424
• Lead Sponsor: Insel Gruppe AG, University Hospital Bern

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-04-22
• Study First Submitted QC: 2021-04-28
• Study First Posted: 2021-05-03
• Study Start: 2021-09-21
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-28
• Last Update Posted: 2024-10-30
• Primary Completion: 2025-07-31
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Age ≥ 65 years
2. 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
3. Selected to undergo transfemoral TAVI based on heart team decision

Exclusion Criteria

1. Life expectancy <1 year irrespective of valvular heart disease
2. Kidney disease with a creatinine clearance ≤30 ml/min
3. Known severe liver disease
4. Known neuromuscular disease
5. Clinically significant anaemia with haemoglobin <80g/L
6. Known inflammatory bowel disease or chronic diarrhea
7. Known ongoing bacterial infection
8. Known galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
9. Current treatment with colchicine, steroids or biologicals for any indication
10. Concomitant intake of Cyclosporine, Amiodarone, Clarithromycin, Erythromycin, Omeprazole, Verapamil or other strong inhibitors of CYP3A4 or P-Glycoprotein
11. Concomitant intake of Carbamazepin, Phenobarbital, Phenytoin, Rifampicin or other strong inductors of CYP3A4 and P-Glycoprotein
12. Permanent pacemaker or implantable cardioverter defibrillator
13. History of atrial fibrillation
14. Absence of sinus rhythm on hospital admission
15. Planned non-cardiac surgery within 30 days
16. Known intolerance to colchicine
17. Inability to provide written informed consent
18. Known or suspected non-compliance, drug or alcohol abuse
19. Participation in another clinical trial with an active intervention
20. Any other planned cardiac intervention performed in the 7 days before TAVI, concomitantly with TAVI or in the 30 days after TAVI except for percutaneous coronary interventions.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Colchicine	Colchicine	-

Primary Outcome Measures

Name	Time	Method
Incidence rate of the composite of new onset atrial fibrillation or occurrence of conduction disturbances requiring the implantation of a permanent pacemaker	30 days	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.

Secondary Outcome Measures

Name	Time	Method
The incidence of conductance disturbances	30 days, 1 year	New or worsened first-degree atrioventricular (AV) block, second-degree AV block (Mobitz I or Mobitz II), high-grade atrioventricular block, third-degree AV block, right bundle branch block, left bundle branch block, left anterior fascicular block, left posterior fascicular block, intraventricular conduction delay
The predictors of conductance disturbances	30 days, 1 year	New or worsened first-degree atrioventricular (AV) block, second-degree AV block (Mobitz I or Mobitz II), high-grade atrioventricular block, third-degree AV block, right bundle branch block, left bundle branch block, left anterior fascicular block, left posterior fascicular block, intraventricular conduction delay
The incidence of new arrhythmias resulting in hemodynamic instability or requiring therapy	30 days, 1 year	Defined as electrical/medical cardioversion or initiation of a new medication e.g. oral anticoagulation, rhythm, or rate controlling therapy
Inflammatory marker levels	at day 1	IL-6, IL-8, TNF-alpha, IL-1β, CRP, high-sensitivity CRP
The incidences of major clinical adverse events	30 days, 1 year	All-cause mortality, stroke, systemic embolism, myocardial infarction, infections, clinical valve thrombosis
Single components of primary composite endpoint	30 days and 1 year	Including predefine sensitivity analysis using the alternative definition of NOAF: At least one episode of atrial fibrillation with a duration \>6 min.
The proportion of prosthetic leaflets with > 50% motion reduction or leaflet thickening	30 days	Based on a study-specific cardiac computed tomography angiography
The proportion of patients with at least one prosthetic leaflet with > 50% motion reduction or with at least one prosthetic leaflet with thickening	30 days	Based on a study-specific cardiac computed tomography angiography

Trial Locations

Locations (1)

Inselspital, Bern University Hospital, Department of Cardiology; 🇨🇭 Bern, Switzerland