Colchicine and Inflammation in Aortic Stenosis (CHIANTI) trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Radboud universitair medisch centrum

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2024-12-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513486-39-00

EudraCT number

2021-005586-40

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To study the effect of colchicine treatment versus placebo on the progression of aortic valve stenosis in patients with moderate aortic valve stenosis.

Conditions and MedDRA coding

Aortic Valve Calcification

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

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

Exclusion criteria 18

1. 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.).
2. A planned aortic valve replacement in the next six months.
3. Severe mitral valve stenosis (MVA < 1cm2).
4. Severe mitral or aortic valve regurgitation.
5. Rheumatic aortic valve disease.
6. Bicuspid aortic valve.
7. Valvular disease due to history of chest radiation.
8. Left ventricular dysfunction (LVEF < 35%).
9. Renal impairment (eGFR <30 ml/min/1.73 m2).
10. Patients aged <50 and >80 years.
11. Pre-existing chronic gastro-intestinal complaints which may obscure signs of colchicine intolerance.
12. Child-bearing potential without the use of contraception.
13. Use of CYP3A4 (e.g. verapamil) or P-glycoprotein inhibitors.
14. Use of bisphosphonate or denosumab.
15. Chronic use of immunosuppressants or anti-inflammatory drugs including colchicine and NSAID's (excl. acetylsalicylic acid).
16. Active or chronic liver disease.
17. The presence of a pacemaker or internal cardiac defibrillator.
18. Life expectancy <2 years.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The change in aortic valve calcium score measured by computed tomography (Agatston Units) at 24 months relative to baseline.

Secondary endpoints 2

1. The change in 18F-NaF uptake of the aortic valve on positron emission tomography at 24 months relative to baseline.
2. The change in peak aortic jet velocity (m/s) measured by echocardiography at 24 months relative to baseline.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Radboud universitair medisch centrum

Sponsor organisation

Stichting Radboud universitair medisch centrum

Address

Geert Grooteplein Zuid 10

City

Nijmegen

Postcode

6525 GA

Country

Netherlands

Scientific contact point

Organisation

Stichting Radboud universitair medisch centrum

Contact name

Saloua El Messaoudi, MD, PhD

Public contact point

Organisation

Stichting Radboud universitair medisch centrum

Contact name

Saloua El Messaoudi, MD, PhD

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications