The Colchicine heart failure preserved trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gentofte Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

18 Jan 2024 → ongoing

Decision date (initial)

2023-09-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

The primary objective of this study is to investigate the effect of colchicine, as compared with placebo, on heart failure related health status using the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS).

Secondary objectives 2

1. To investigate the effect of colchicine, as compared to placebo, on heart failure related health status using the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS).
2. To investigate the effect of colchicine on the proportion of patients with a ≥ 5-point increase in KCCQ-CS and KCCQ-OS compared to placebo.

Conditions and MedDRA coding

Heart failure with preserved ejection fraction (HFpEF)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age ≥ 40 years
2. LVEF ≥ 45% by echocardiography during the screening epoch or within 6 months prior to screening visit
3. Symptom(s) of heart failure for at least 30 days prior to screening visit and current symptoms of heart failure (NYHA functional class II-IV) at screening visit
4. Objective evidence of cardiac structural and/or functional abnormalities consistent with the presence of LV diastolic dysfunction/raised LV filling pressures (left atrial enlargement and/or left ventricular hypertrophy) judged by echocardiography at screening epoch or within 12 months prior to screening visit
5. Raised pro-BNP ≥ 125 pg/ml (sinus rhythm) or ≥ 300 pg/ml (atrial fibrillation (AF))
6. Body Mass Index (BMI) < 40 kg/m2 at screening visit
7. Female patients should either not be of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile, or of childbearing potential and practicing one of the following methods of contraception throughout the study and for 30 days after study completion: Hormonal contraception (oral contraceptives, contraceptive implant, injectable birth control, contraceptive patch, or vaginal ring) or intrauterine device
8. Patients will have given written, informed consent and are able and willing to comply with the requirements of the study protocol

Exclusion criteria 27

1. Colchicine treatment for another cause, e.g., gout
2. Allergy/hypersensitivity to colchicine
3. Uncontrolled hypertension (systolic BP >180 mmHg or diastolic BP >110 mmHg)
4. History of malignancy of any organ system within the past 5 years excluding a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma, localized prostate cancer and/or localized carcinoma in situ of the cervix
5. Cirrhosis, chronic active hepatitis, or other severe hepatic disease
6. Hemodialysis
7. Estimated glomerular filtration rate (eGFR) < 35 mL/min/1.73 m2
8. Systemic treatment with moderate or strong cytochrome P450 3A4 (CYP3A4) inhibitors or P-glycoprotein inhibitors
9. Anemia, thrombocytopenia, or leucopenia defined as any of the following measurements within the last 3 months: Hemoglobin < 7 mmol/L, Platelet count < 110 x 10˄9/L, White blood cell count < 3.0 x 10˄9/L
10. Acute decompensated heart failure (hospitalization for heart failure within 7 days prior to screening visit)
11. Acute coronary syndrome (including MI), cardiac surgery, other major cardiovascular surgery, ablation of atrial flutter/fibrillation, valve repair/replacement, implanted cardioverter defibrillator or urgent PCI within 3 months prior to screening visit or an elective PCI within 30 days prior to screening visit
12. Planned coronary revascularization (percutaneous intervention or surgical), major cardiac surgery (coronary artery bypass grafting, valve repair/replacement, ventricular assist device, cardiac transplantation, or any other surgery requiring thoracotomy), CRT or ablation of atrial flutter/fibrillation during the trial
13. Any clinical event within 6 months prior to screening visit that could have reduced LVEF (e.g., MI, CABG), unless echocardiographic measurement was performed after the event confirming LVEF ≥ 45%
14. Stroke, transient ischemic attack, carotid surgery, or carotid angioplasty within 3 months prior to screening visit
15. Previous cardiac transplantation, complex congenital heart disease or cardiac resynchronization therapy
16. Heart failure due to any of the following: known infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac tamponade, known genetic hypertrophic cardiomyopathy, obstructive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy or uncorrected severe/hemodynamically significant valvular heart disease
17. Life threatening or uncontrolled dysrhythmia, including symptomatic or sustained ventricular tachycardia and AF or atrial flutter with a resting ventricular rate > 110 beats per minute
18. Evidence of right-sided HF in the absence of left sided structural heart disease
19. Probable alternative diagnosis that in the opinion of the investigator could account for the patient’s HF symptoms (i.e., anemia, hypothyroidism, severe obesity)
20. World Health Organization Group 1 pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease, including COPD (i.e., requiring home oxygen, chronic nebulizer therapy or chronic oral steroid therapy, or hospitalization for exacerbation of COPD requiring ventilatory assist within 12 months prior to enrollment)
21. Female patients who are pregnant, lactating, or considering becoming pregnant during the study or for 6 months after study completion
22. Significant drug or alcohol abuse during the last year
23. Current use of or plans to initiate chronic systemic steroid therapy during the study (topical or inhaled steroids are allowed)
24. Chronic inflammatory bowel disease (Crohn’s disease or ulcerative colitis) or chronic diarrhea
25. Use of other investigational drugs within 30 days of the time of enrollment
26. Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study
27. Life expectancy < 2 years at the screening visit

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To investigate the effect of colchicine, as compared with placebo, on heart failure related health status using the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS)

Secondary endpoints 2

1. To investigate the effect of colchicine, as compared to placebo, on heart failure related health status using the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS).
2. To investigate the effect of colchicine on the proportion of patients with a ≥ 5-point increase in KCCQ-CS and KCCQ-OS compared to placebo

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gentofte Hospital

Sponsor organisation

Gentofte Hospital

Address

Gentofte Hospitalsvej 1

City

Hellerup

Postcode

2900

Country

Denmark

Scientific contact point

Organisation

Gentofte Hospital

Contact name

Trial site

Public contact point

Organisation

Gentofte Hospital

Contact name

Trial site

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 11 files

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

Application history

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