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Colchicine and Inflammation in Aortic Stenosis (CHIANTI)

Primary Purpose

Aortic Valve Disease, Aortic Valve Stenosis, Aortic Valve Calcification

Status
Recruiting
Phase
Phase 3
Locations
Netherlands
Study Type
Interventional
Intervention
Colchicine
Placebo
Sponsored by
Radboud University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aortic Valve Disease focused on measuring Aortic Stenosis, Inflammation

Eligibility Criteria

50 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criterion:

• Asymptomatic moderate aortic valve stenosis on recent (<6 months) echocardiography (based on peak velocity, mean gradient, aortic valve area). The severity of AS will be quantified according to current EACVI / ASE guidelines.

Exclusion Criteria:

  • Heavily calcified aortic valve on echocardiography (defined as grade 4 calcification: extensive thickening/calcification of all cusps as described in the articles by Rosenhek et al.);
  • a planned aortic valve replacement in the next six months;
  • severe mitral valve stenosis (MVA < 1cm2);
  • severe mitral or aortic valve regurgitation;
  • rheumatic aortic valve disease;
  • bicuspid aortic valve;
  • valvular disease due to history of chest radiation;
  • left ventricular dysfunction (LVEF < 35%);
  • renal impairment (eGFR <30 ml/min/1.73m2);
  • patients aged <50 and >80 years;
  • pre-existing chronic gastro-intestinal complaints which may obscure signs of colchicine intolerance;
  • child-bearing potential without the use of contraception;
  • use of CYP3A4 (e.g. verapamil) or P-glycoprotein inhibitors;
  • use of bisphosphonate or denosumab;
  • chronic use of immunosuppressants or anti-inflammatory drugs including colchicine and NSAID's (excl. acetylsalicylic acid);
  • active or chronic liver disease;
  • the presence of a pacemaker or internal cardiac defibrillator;
  • life expectancy <2 years.

Sites / Locations

  • RadboudumcRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Colchicine

Placebo

Arm Description

75 patients will receive colchicine tablets

75 patients will receive placebo tablets

Outcomes

Primary Outcome Measures

Change in aortic valve calcium score
Change in aortic valve calcium score measured by computed tomography aortic valve calcification (CT-AVC).

Secondary Outcome Measures

Aortic valve 18F-NaF uptake
Difference in aortic valve 18F-NaF uptake of the aortic valve using positron emission tomography (PET) between baseline and end of study.
Change in echocardiographic parameter for aortic stenosis
Determined by change in peak velocity (m/s)
Adverse Outcomes
Determine the effect of colchicine on calcified aortic stenosis related adverse outcomes (cardiac death, myocardial infarction, stroke, (hospitalization for) heart failure and aortic valve replacement).

Full Information

First Posted
November 16, 2021
Last Updated
January 8, 2023
Sponsor
Radboud University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT05162742
Brief Title
Colchicine and Inflammation in Aortic Stenosis
Acronym
CHIANTI
Official Title
Does Colchicine Reduce Progression of Aortic Valve Stenosis?
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 22, 2022 (Actual)
Primary Completion Date
December 22, 2025 (Anticipated)
Study Completion Date
December 22, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radboud University Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

Brief Summary
Aortic stenosis (AS) is the most common valvular heart disease in the developed world. Once symptomatic, untreated patients have a poor prognosis with five-year survival rate of 25%. Once at an advanced stage, AS will lead to the development of left ventricle hypertrophy, and eventually heart failure and death. At-present, there is no effective medical therapy for aortic stenosis. Current management of patients with AS consists of 'watchful waiting'. Valve replacement is needed when these patients (often acutely) become symptomatic. Recent studies have shown that inflammatory processes with similarities to atherosclerosis play an important role in AS. Therefore, we hypothesize that treatment with anti-inflammatory therapy, in the form of colchicine, could reduce the progression of AS. If positive, this trial will be the first to provide a potential therapeutic option for millions of people world-wide with AS.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aortic Valve Disease, Aortic Valve Stenosis, Aortic Valve Calcification, Inflammation, Calcification, Cardiovascular Diseases
Keywords
Aortic Stenosis, Inflammation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Colchicine
Arm Type
Active Comparator
Arm Description
75 patients will receive colchicine tablets
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
75 patients will receive placebo tablets
Intervention Type
Drug
Intervention Name(s)
Colchicine
Intervention Description
ATC: M04AC01
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo tablets
Primary Outcome Measure Information:
Title
Change in aortic valve calcium score
Description
Change in aortic valve calcium score measured by computed tomography aortic valve calcification (CT-AVC).
Time Frame
Baseline and 24 months
Secondary Outcome Measure Information:
Title
Aortic valve 18F-NaF uptake
Description
Difference in aortic valve 18F-NaF uptake of the aortic valve using positron emission tomography (PET) between baseline and end of study.
Time Frame
Baseline and 24 months
Title
Change in echocardiographic parameter for aortic stenosis
Description
Determined by change in peak velocity (m/s)
Time Frame
Baseline, 12 months and 24 months
Title
Adverse Outcomes
Description
Determine the effect of colchicine on calcified aortic stenosis related adverse outcomes (cardiac death, myocardial infarction, stroke, (hospitalization for) heart failure and aortic valve replacement).
Time Frame
Baseline and 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criterion: • Asymptomatic moderate aortic valve stenosis on recent (<6 months) echocardiography (based on peak velocity, mean gradient, aortic valve area). The severity of AS will be quantified according to current EACVI / ASE guidelines. Exclusion Criteria: Heavily calcified aortic valve on echocardiography (defined as grade 4 calcification: extensive thickening/calcification of all cusps as described in the articles by Rosenhek et al.); a planned aortic valve replacement in the next six months; severe mitral valve stenosis (MVA < 1cm2); severe mitral or aortic valve regurgitation; rheumatic aortic valve disease; bicuspid aortic valve; valvular disease due to history of chest radiation; left ventricular dysfunction (LVEF < 35%); renal impairment (eGFR <30 ml/min/1.73m2); patients aged <50 and >80 years; pre-existing chronic gastro-intestinal complaints which may obscure signs of colchicine intolerance; child-bearing potential without the use of contraception; use of CYP3A4 (e.g. verapamil) or P-glycoprotein inhibitors; use of bisphosphonate or denosumab; chronic use of immunosuppressants or anti-inflammatory drugs including colchicine and NSAID's (excl. acetylsalicylic acid); active or chronic liver disease; the presence of a pacemaker or internal cardiac defibrillator; life expectancy <2 years.
Facility Information:
Facility Name
Radboudumc
City
Nijmegen
State/Province
The Netherlands
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Saloua El Messaoudi, MD, PhD
Phone
+31(0)24 3616785
Email
onderzoek.cardio@radboudumc.nl
First Name & Middle Initial & Last Name & Degree
Saloua El Messaoudi, MD, PhD
First Name & Middle Initial & Last Name & Degree
Nieky Mohammadnia, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Colchicine and Inflammation in Aortic Stenosis

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