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

Primary Purpose

Transcatheter Aortic Valve Replacement, Atrial Fibrillation New Onset, Pacemaker

Status

Recruiting

Phase

Phase 3

Locations

Switzerland

Study Type

Interventional

Intervention

Colchicine

Placebo

About this trial

This is an interventional prevention trial for Transcatheter Aortic Valve Replacement

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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
Known intolerance to colchicine
Inability to provide written informed consent
Known or suspected non-compliance, drug or alcohol abuse
Participation in another clinical trial with an active intervention
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.

Sites / Locations

Inselspital, Bern University Hospital, Department of CardiologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Colchicine

Placebo

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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

The predictors of conductance disturbances

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

Inflammatory marker levels

IL-6, IL-8, TNF-alpha, IL-1β, CRP, high-sensitivity CRP

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

The proportion of prosthetic leaflets with > 50% motion reduction or leaflet thickening

Based on a study-specific cardiac computed tomography angiography

The incidences of major clinical adverse events

All-cause mortality, stroke, systemic embolism, myocardial infarction, infections, clinical valve thrombosis

Full Information

NCT ID

NCT04870424

First Posted

April 22, 2021

Last Updated

January 23, 2023

Sponsor

Insel Gruppe AG, University Hospital Bern

1. Study Identification

Unique Protocol Identification Number

NCT04870424

Brief Title

Colchicine for Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement

Acronym

Co-STAR

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Recruiting

Study Start Date

September 21, 2021 (Actual)

Primary Completion Date

July 31, 2025 (Anticipated)

Study Completion Date

June 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Insel Gruppe AG, University Hospital Bern

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Colchicine

Arm Type

Experimental

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Colchicine

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

30 days

Secondary Outcome Measure Information:

Title

Single components of primary composite endpoint

Description

Including predefine sensitivity analysis using the alternative definition of NOAF: At least one episode of atrial fibrillation with a duration >6 min.

Time Frame

30 days and 1 year

Title

The incidence of conductance disturbances

Description

Time Frame

30 days, 1 year

Title

The predictors of conductance disturbances

Description

Time Frame

30 days, 1 year

Title

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

Description

Defined as electrical/medical cardioversion or initiation of a new medication e.g. oral anticoagulation, rhythm, or rate controlling therapy

Time Frame

30 days, 1 year

Title

Inflammatory marker levels

Description

IL-6, IL-8, TNF-alpha, IL-1β, CRP, high-sensitivity CRP

Time Frame

at day 1

Title

The proportion of patients with at least one prosthetic leaflet with > 50% motion reduction or with at least one prosthetic leaflet with thickening

Description

Based on a study-specific cardiac computed tomography angiography

Time Frame

30 days

Title

The proportion of prosthetic leaflets with > 50% motion reduction or leaflet thickening

Description

Based on a study-specific cardiac computed tomography angiography

Time Frame

30 days

Title

The incidences of major clinical adverse events

Description

All-cause mortality, stroke, systemic embolism, myocardial infarction, infections, clinical valve thrombosis

Time Frame

30 days, 1 year

Other Pre-specified Outcome Measures:

Title

Safety Outcome

Description

Incidence of gastrointestinal side effects and clinically severe side effects possibly related to study drug intake

Time Frame

30 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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 Known intolerance to colchicine Inability to provide written informed consent Known or suspected non-compliance, drug or alcohol abuse Participation in another clinical trial with an active intervention 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Thomas Pilgrim, Prof.

Phone

+41 31 632 08 27

thomas.pilgrim@insel.ch

First Name & Middle Initial & Last Name or Official Title & Degree

Jonas Lanz, Dr. med.

Phone

+41 31 632 21 11

jonas.lanz@insel.ch

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Thomas Pilgrim, Prof.

Organizational Affiliation

University of Bern, Switzerland

Official's Role

Principal Investigator

Facility Information:

Facility Name

Inselspital, Bern University Hospital, Department of Cardiology

City

Bern

ZIP/Postal Code

3010

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Thomas Pilgrim, Prof.

Phone

+41 31 632 08 27

thomas.pilgrim@insel.ch

First Name & Middle Initial & Last Name & Degree

Jonas Lanz, Dr. med.

Phone

+41 31 632 21 11

jonas.lanz@insel.ch

First Name & Middle Initial & Last Name & Degree

Thomas Pilgrim, Prof.

First Name & Middle Initial & Last Name & Degree

Christoph Ryffel, Dr. med.

First Name & Middle Initial & Last Name & Degree

Jonas Lanz, Dr. med.

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Colchicine for Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement

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