Clinical trial NCT06837623: Role of Colchicine as Anti-Inflammatory Therapy in HFpEF
Official title: The Role of Colchicine as Anti-Inflammatory Treatment in Patients With HFpEF: A Prospective Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: HFpEF - Heart Failure With Preserved Ejection Fraction
Keywords: HFpEF
Colchicine
Lead sponsor: Cairo University
Sponsor class: OTHER
First posted: 2025-02-20
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Heart failure with preserved ejection fraction (HFpEF) is a condition associated with high morbidity and mortality. Chronic low-grade inflammation plays a key role in its progression, yet few treatments specifically target this pathway.

This clinical trial aims to evaluate the effectiveness of colchicine, a well-tolerated anti-inflammatory drug, in reducing inflammation in HFpEF patients. The study will assess whether colchicine lowers levels of soluble ST2 (sST2), a biomarker linked to inflammation and cardiac stress in HFpEF.

Participants will take colchicine daily for three months, with blood samples collected at baseline and at the end of the study to measure changes in sST2 levels. The findings could provide new insights into the potential role of colchicine as a treatment for HFpEF.

Detailed description: Heart failure with preserved ejection fraction (HFpEF) is a complex condition associated with high morbidity and mortality. While its exact causes remain unclear, low-grade systemic inflammation plays a key role by promoting myocardial fibrosis and increasing heart muscle stiffness. Despite this, anti-inflammatory treatments for HFpEF remain largely unexplored.

Colchicine is a well-established anti-inflammatory drug that blocks key inflammatory pathways, including inflammasome activation and the release of interleukin-1 (IL-1). It has demonstrated cardiovascular benefits in trials such as COLCOT and LoDoCo2, significantly reducing the risk of heart-related events in coronary artery disease. However, its effects in HFpEF patients are not yet known.

Two important biomarkers-soluble suppression of tumorigenicity 2 (sST2) and high-sensitivity C-reactive protein (hsCRP)-are strongly linked to worse outcomes in HFpEF. Elevated sST2 reflects increased fibrosis and cardiac stress, while high hsCRP indicates systemic inflammation. Both markers are associated with more severe symptoms and a higher risk of complications. Additionally, the 6-minute walk test (6MWT) is a widely used measure of physical function and exercise capacity in heart failure patients.

This single-center, prospective clinical trial aims to evaluate the effects of colchicine in HFpEF patients with elevated inflammation. Participants will receive colchicine for three months, with assessments of sST2, hsCRP, and 6MWT performance before and after treatment. Findings from this study may provide valuable insights into whether colchicine can reduce inflammation and improve functional capacity in HFpEF patients.

Eligibility criteria: Inclusion Criteria:

* Adult ≥ 18 years of age, males and females.
* Left Ventricular Ejection Fraction (LVEF) ≥ 50%.
* Symptoms and/or signs of heart failure.
* H2FPEF score ≥ 6 points or HFA-PEFF score ≥ 5 points.
* N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥125 pg/mL at baseline (patients with atrial fibrillation at baseline NT-proBNP ≥365 pg/mL), or objective evidence of systemic or pulmonary congestion.
* Stable medical therapy within the last 1 month.

Exclusion Criteria:

* Patients requiring colchicine for other conditions or with a history of colchicine intolerance or hypersensitivity.
* Active or chronic inflammatory diseases or infection.
* Presence of active solid tumors or hematological malignancies.
* Estimated glomerular filtration rate (eGFR) \<35 mL/min/1.73 m².
* Severe liver disease includes Child-Pugh class B or C, cirrhosis, or chronic active hepatitis.
* Concurrent use of strong CYP3A4 or P-glycoprotein inhibitors.
* Presence of blood dyscrasias.
* Recent major cardiovascular events or procedures within the last 3 months.
* Established diagnosis of pericardial disease, myocarditis, hypertrophic cardiomyopathy, and cardiac amyloidosis
* Significant valvular heart disease.
* Lack of informed consent.

Primary outcomes:
measure: Change in Soluble Suppression of Tumourigenicity 2 (sST2,ng/ml)
timeFrame: From baseline to 12 weeks post-treatment initiation
Secondary outcomes:
measure: Change in high-sensitivity C-reactive protein (hsCRP, mg/L)
timeFrame: From baseline to 12 weeks post-treatment initiation
measure: Change in 6 Minute Walk Test (6MWT,meters)
timeFrame: From baseline to 12 weeks post-treatment initiation
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Cairo University - Kasr Al-Ainy
Study officials:
affiliation: Cairo University
name: Magdy Abdelhamid Abdel Aziz, Professor of Cardivascular M
role: STUDY_CHAIR
affiliation: Cairo University
name: Ahmed Kamal, MD in Cardiology
role: PRINCIPAL_INVESTIGATOR
affiliation: Cairo University
name: Nesrine M El Gharbawi, Prof of clin. & Chem Patho
role: PRINCIPAL_INVESTIGATOR
affiliation: Cairo University
name: Shaima M Zeyad, Cardiology Resident
role: PRINCIPAL_INVESTIGATOR
References: