Clinical trial NCT04870424: Colchicine for Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement
Official title: Colchicine for Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement (Co-STAR): a Randomized-controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Transcatheter Aortic Valve Replacement
Atrial Fibrillation New Onset
Pacemaker
Colchicine
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2021-05-03
Enrollment: 120
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence rate of the composite of new onset atrial fibrillation or occurrence of conduction disturbances requiring the implantation of a permanent pacemaker
timeFrame: 30 days
Secondary outcomes:
measure: Single components of primary composite endpoint
timeFrame: 30 days and 1 year
measure: The incidence of conductance disturbances
timeFrame: 30 days, 1 year
measure: The predictors of conductance disturbances
timeFrame: 30 days, 1 year
measure: The incidence of new arrhythmias resulting in hemodynamic instability or requiring therapy
timeFrame: 30 days, 1 year
measure: Inflammatory marker levels
timeFrame: at day 1
measure: The proportion of patients with at least one prosthetic leaflet with > 50% motion reduction or with at least one prosthetic leaflet with thickening
timeFrame: 30 days
measure: The proportion of prosthetic leaflets with > 50% motion reduction or leaflet thickening
timeFrame: 30 days
measure: The incidences of major clinical adverse events
timeFrame: 30 days, 1 year
Other outcomes:
measure: Safety Outcome
timeFrame: 30 days
Locations:
city: Bern
country: Switzerland
facility: Inselspital, Bern University Hospital, Department of Cardiology
Study officials:
affiliation: University of Bern, Switzerland
name: Thomas Pilgrim, Prof.
role: PRINCIPAL_INVESTIGATOR
References: