Colchicine in Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

May 2, 2023 updated by: I.M. Sechenov First Moscow State Medical University
Heart failure with preserved left ventricular ejection fraction (HFpEF) is a syndrome associated with high morbidity and mortality rates. Systemic low-grade inflammation is acknowledged to be a fundamental pathophysiological mechanism of HFpEF. Interventions targeting inflammatory pathway is understudied in HFpEF. Colchicine is a safe and well tolerated anti-inflammatory drug, which interferes with several steps in the inflammatory process. The drug has been extensively studied in different cardiovascular pathologies except HFpEF. We assume that colchicine decreases inflammation and reduces sST2 levels in HFpEF.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

HFpEF is a syndrome associated with high morbidity and mortality rates. The underlying mechanisms of the syndrome are not fully understood. Systemic low-grade inflammation is acknowledged to be a fundamental pathophysiological mechanism of HFpEF, which facilitates cardiomyocyte stiffness and myocardial fibrosis development. However, anti-inflammatory treatment approaches are largely under studied. Colchicine is a safe and well tolerated anti-inflammatory drug, which interferes with several steps in the inflammatory process, resulting in suppression of a number of pro-inflammatory pathways and cytokines release, including IL-1, hsCRP. The drug has been extensively studied in patients with coronary artery disease (COLCOT, LoDoCo2) and showed significant reduction in risk of cardio-vascular events, as well as inflammation. Post-hoc analysis of in the CANTOS study investigated the effect of monoclonal antibody targeting interleukin-1β in patients with prior myocardial infarction, showed a reduction in heart failure (HF) hospitalization of patients with elevations in high-sensitivity C-reactive protein (hsCRP). There is no data available regarding the effect of Colchicine on HFpEF patients. Soluble suppression of tumourigenicity 2 (sST2), a member of the interleukin (IL)-1 receptor family, which is not restricted to inflammation, but is also expressed in cardiomyocytes, fibroblast and endothelial cells of cardiac microvessels in response to myocardial stress antagonizing cardioprotective effects of IL-33/ST2 system. In HFpEF, sST2 associated with worse clinical signs and symptoms, co-morbidities, biomarkers of fibrosis and neurohormonal activation. Elevated levels of sST2 are acknowledged as a predictor of worse prognosis in both HF with reduced ejection fraction (HFrEF) and HFpEF. We assume that colchicine decreases inflammation and reduces sST2 levels in HFpEF.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 40 years of age, male and female
  • Left ventricular ejection fraction (LVEF) ≥ 50%
  • Symptoms and signs of heart failure
  • N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥300 pg/ml at baseline (patients in atrial fibrillation at baseline NT-proBNP ≥ 600 pg/ml), left atrial volume index (LAVI) >34 mL/m2 or a left ventricular mass index (LVMI) =115 g/m2 for males and =95 g/m2 for females
  • body mass index (BMI) > 30kg/m2 or diabetes mellitus

Exclusion Criteria:

  • Hypertrophic cardiomyopathy, constrictive pericarditis, or cardiac amyloidosis
  • Acute decompensation of HF in the last 1 month
  • Valvular heart disease
  • Prior history of LVEF below 50%
  • Acute myocardial infarction in the last 3 months, cardiac surgery or cerebrovascular accident within the recent 6 months
  • Any active or chronic inflammatory diseases or infections
  • Patients with indication for colchicine therapy or history of colchicine intolerance
  • Severe hepatic (alanine aminotransferase N3 upper limit of normal or renal dysfunction (estimated glomerular filtration rate <45 mL/min per 1.73m2)
  • Severe nervous system diseases
  • History of any malignancy or suffering from cancer
  • Lack of informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Colchicine 0.5 bid
Eligible HFpEF patients will be randomized in 1:1 ratio by an investigator with either colchicine 0.5 twice daily or usual care for 12 weeks
Drug: Colchicine
The active treatment intervention consists of colchicine 0.5 mg twice daily that will be administrated by the investigator
No Intervention: Usual Care
Eligible HFpEF patients will be randomized in 1:1 ratio by an investigator with either colchicine 0.5 twice daily or usual care for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Soluble suppression of tumourigenicity 2 (sST2,ng/ml)
Time Frame: from baseline to 12 weeks of treatment
Delta_circulating sST2
from baseline to 12 weeks of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in high-sensitivity C-reactive protein (hsCRP, mg/l )
Time Frame: from baseline to 12 weeks of treatment
Delta_ circulating hsCRP
from baseline to 12 weeks of treatment
Change in N-terminal pro-brain natriuretic peptide (NTproBNP, ng,ml)
Time Frame: from baseline to 12 weeks of treatment
Delta_circulating NTproBNP
from baseline to 12 weeks of treatment
Change in E/e' (average)
Time Frame: from baseline to 12 weeks of treatment
Delta_ E/e' (average) by 2D- echocardiography
from baseline to 12 weeks of treatment
Change in Left ventricular global longitudinal strain (LVGLS,%)
Time Frame: from baseline to 12 weeks of treatment
Delta_ left ventricular global longitudinal strain by 2D speckle tracking-echocardiography
from baseline to 12 weeks of treatment
Left atrial reservoir strain (LA reservoir strain ,%)
Time Frame: from baseline to 12 weeks of treatment
Delta_ LA reservoir strain by 2D speckle tracking-echocardiography
from baseline to 12 weeks of treatment
Drug discontinuation
Time Frame: during 12 weeks of treatment
Frequency of drug discontinuation
during 12 weeks of treatment
Incidence of side effects
Time Frame: during 12 weeks of treatment
Side effects will be registered and include gastrointestinal symptoms, hepatotoxicity, muscle weakness or pain, myotoxicity, renal dysfunction
during 12 weeks of treatment
Change in insulin-like growth factor-binding protein 7 (IGFBP-7, ng/ml)
Time Frame: from baseline to 12 weeks of treatment
Delta_circulating IGFBP-7
from baseline to 12 weeks of treatment
Change in procollagen type I carboxy-terminal propeptide (PICP, ng/ml)
Time Frame: from baseline to 12 weeks of treatment
Delta_circulating PICP
from baseline to 12 weeks of treatment
Change in C-terminal telopeptide of collagen type I (CITP,ng/ml)
Time Frame: from baseline to 12 weeks of treatment
Delta_circulating CITP
from baseline to 12 weeks of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

I.M. Sechenov First Moscow State Medical University

Investigators

  • Principal Investigator: Anastasia Shchendrygina, Sechenov Univerity

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 15, 2022

Primary Completion (Anticipated)

June 1, 2024

Study Completion (Anticipated)

November 1, 2024

Study Registration Dates

First Submitted

November 5, 2022

First Submitted That Met QC Criteria

November 24, 2022

First Posted (Actual)

December 5, 2022

Study Record Updates

Last Update Posted (Actual)

May 3, 2023

Last Update Submitted That Met QC Criteria

May 2, 2023

Last Verified

August 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 03-22

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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