Colchicine for Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement

Transcatheter Aortic Valve Replacement Clinical Trial

— Co-STAR  

Official title:

Colchicine for Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement (Co-STAR): a Randomized-controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04870424
• Other study ID #: Co-STAR
• Status: Recruiting
• Phase: Phase 3
• Start date: September 21, 2021
• Est. completion date: June 30, 2026

Study information

• Verified date: May 2024
• Source: Insel Gruppe AG, University Hospital Bern
• Contact: Thomas Pilgrim, Prof.
• Phone: +41 31 632 08 27
• Email: thomas.pilgrim[@]insel.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: June 30, 2026
• Est. primary completion date: July 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Atrial Fibrillation
• Atrial Fibrillation New Onset
• Colchicine
• Pacemaker
• Transcatheter Aortic Valve Replacement

Intervention

Drug:
• Colchicine
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.
• Placebo
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.

Locations

Country	Name	City	State
Switzerland	Inselspital, Bern University Hospital, Department of Cardiology	Bern

Sponsors (1)

Lead Sponsor	Collaborator
Insel Gruppe AG, University Hospital Bern

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety Outcome	Incidence of gastrointestinal side effects and clinically severe side effects possibly related to study drug intake	30 days
Primary	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	Single components of primary composite endpoint	Including predefine sensitivity analysis using the alternative definition of NOAF: At least one episode of atrial fibrillation with a duration >6 min.	30 days and 1 year
Secondary	The incidence of conductance disturbances	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	30 days, 1 year
Secondary	The predictors of conductance disturbances	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	30 days, 1 year
Secondary	The incidence of new arrhythmias resulting in hemodynamic instability or requiring therapy	Defined as electrical/medical cardioversion or initiation of a new medication e.g. oral anticoagulation, rhythm, or rate controlling therapy	30 days, 1 year
Secondary	Inflammatory marker levels	IL-6, IL-8, TNF-alpha, IL-1ß, CRP, high-sensitivity CRP	at day 1
Secondary	The proportion of patients with at least one prosthetic leaflet with > 50% motion reduction or with at least one prosthetic leaflet with thickening	Based on a study-specific cardiac computed tomography angiography	30 days
Secondary	The proportion of prosthetic leaflets with > 50% motion reduction or leaflet thickening	Based on a study-specific cardiac computed tomography angiography	30 days
Secondary	The incidences of major clinical adverse events	All-cause mortality, stroke, systemic embolism, myocardial infarction, infections, clinical valve thrombosis	30 days, 1 year