Colchicine for Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement (Co-STAR)

• ClinicalTrials.gov Identifier: NCT04870424
• Recruitment Status: Recruiting
• First Posted: May 3, 2021
• Last Update Posted: October 22, 2021
• Sponsor: University Hospital Inselspital, Berne
• Information provided by (Responsible Party): University Hospital Inselspital, Berne

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Transcatheter Aortic Valve Replacement; Atrial Fibrillation New Onset; Pacemaker; Colchicine	Drug: Colchicine; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Colchicine for Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement (Co-STAR): a Randomized-controlled Trial
• Actual Study Start Date: September 21, 2021
• Estimated Primary Completion Date: July 31, 2024
• Estimated Study Completion Date: June 30, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Colchicine	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 Comparator: Placebo	Drug: 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.

Outcome Measures

Primary Outcome Measures :

1. Incidence rate of the composite of new onset atrial fibrillation or occurrence of conduction disturbances requiring the implantation of a permanent pacemaker [ Time Frame: 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 :

1. Single components of primary composite endpoint [ Time Frame: 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.
2. The incidence of conductance disturbances [ Time Frame: 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
3. The predictors of conductance disturbances [ Time Frame: 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
4. The incidence of new arrhythmias resulting in hemodynamic instability or requiring therapy [ Time Frame: 30 days, 1 year ]
   Defined as electrical/medical cardioversion or initiation of a new medication e.g. oral anticoagulation, rhythm, or rate controlling therapy
5. Inflammatory marker levels [ Time Frame: at day 1 ]
   IL-6, IL-8, TNF-alpha, IL-1β, CRP, high-sensitivity CRP
6. The proportion of patients with at least one prosthetic leaflet with > 50% motion reduction or with at least one prosthetic leaflet with thickening [ Time Frame: 30 days ]
   Based on a study-specific cardiac computed tomography angiography
7. The proportion of prosthetic leaflets with > 50% motion reduction or leaflet thickening [ Time Frame: 30 days ]
   Based on a study-specific cardiac computed tomography angiography
8. The incidences of major clinical adverse events [ Time Frame: 30 days, 1 year ]
   All-cause mortality, stroke, systemic embolism, myocardial infarction, infections, clinical valve thrombosis

Other Outcome Measures:

1. Safety Outcome [ Time Frame: 30 days ]
   Incidence of gastrointestinal side effects and clinically severe side effects possibly related to study drug intake

Eligibility Criteria

• Ages Eligible for Study: 65 Years and older (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Contacts

Contact: Thomas Pilgrim, Prof.; +41 31 632 08 27; thomas.pilgrim@insel.ch

Contact: Jonas Lanz, Dr. med.; +41 31 632 21 11; jonas.lanz@insel.ch

Locations

Switzerland

Inselspital, Bern University Hospital, Department of Cardiology; Recruiting

Bern, Switzerland, 3010

Contact: Thomas Pilgrim, Prof. +41 31 632 08 27 thomas.pilgrim@insel.ch

Contact: Jonas Lanz, Dr. med. +41 31 632 21 11 jonas.lanz@insel.ch

Principal Investigator: Thomas Pilgrim, Prof.

Sub-Investigator: Christoph Ryffel, Dr. med.

Sub-Investigator: Jonas Lanz, Dr. med.

Sponsors and Collaborators

University Hospital Inselspital, Berne

Investigators

• Principal Investigator: Thomas Pilgrim, Prof.; University of Bern, Switzerland

More Information

• Responsible Party: University Hospital Inselspital, Berne
• ClinicalTrials.gov Identifier: NCT04870424
• Other Study ID Numbers: Co-STAR
• First Posted: May 3, 2021
• Last Update Posted: October 22, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Atrial Fibrillation; Aortic Valve Stenosis; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Colchicine; Gout Suppressants; Antirheumatic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents