Effects of Pioglitazone in Calcific Aortic Valve Disease

Sponsor

Wuhan Union Hospital, China (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05875675

Collaborator

(none)

100

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This is a prospective, randomized, comparative, clinical trial conducted by Wuhan Union Hospital that aims to evaluate the efficacy and safety of pioglitazone compared to placebo in patients with calcific aortic valve disease with mild aortic valve stenosis.

Condition or Disease	Intervention/Treatment	Phase
Calcification of Aortic Valve Aortic Valve Stenosis	Drug: Drug: Pioglitazone Oral Tablet Dietary Supplement: Placebo	Phase 2

Detailed Description

Pioglitazone is an oral drug for the treatment of type 2 diabetes that improves the utilization of glucose by the body by inhibiting hepatic gluconeogenesis, and has anti-inflammatory and antioxidant effects that may improve vascular endothelial cell injury and prevent cardiovascular disease. This study is to slow the process of aortic valve calcification by pioglitazone intervention with the aim of reducing the risk of aortic valve stenosis. Participants were randomized into two groups: one group was given oral pioglitazone treatment and the other group was given placebo control. Patients in both groups were observed for aortic valve calcification during the follow-up period, and changes in aortic valve thickness, degree of calcification, and flow were recorded by cardiac ultrasonography, while the incidence of cardiovascular events and adverse effects were assessed.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Prevention

Official Title:

Effect of Pioglitazone Treatment in Patient's Calcific Aortic Valve Disease With Mild Aortic Valve Stenosis

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Jul 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Drug group Dietary Supplement: Pioglitazone 30 mg by mouth daily	Drug: Drug: Pioglitazone Oral Tablet Dietary Supplement: Pioglitazone 30 mg by mouth daily
Placebo Comparator: Control group Dietary Supplement: Placebo	Dietary Supplement: Placebo Dietary: Supplement: Placebo

Arm

Intervention/Treatment

Experimental: Drug group

Dietary Supplement: Pioglitazone 30 mg by mouth daily

Drug: Drug: Pioglitazone Oral Tablet

Dietary Supplement: Pioglitazone 30 mg by mouth daily

Placebo Comparator: Control group

Dietary Supplement: Placebo

Dietary Supplement: Placebo

Dietary: Supplement: Placebo

Outcome Measures

Primary Outcome Measures

overall survival [3 years]
overall survival (OS)

Secondary Outcome Measures

Time-to-major adverse cardiovascular events [104 weeks]
Time-to-major adverse cardiovascular events of cardiac death, non- fatal myocardial infarction, heart failure hospitalization and stroke
Change in aortic valve stenosis severity [at week 104]
Change in aortic valve stenosis severity as measured by peak transaortic velocity using echocardiography at week 104 as compared to baseline
HbA1c [104 weeks]
Metabolic control
Glucose level [104 weeks]
Metabolic control

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female adult ≥ 35 years of age at the time of rescruiting.
Subject has calcific aortic valve disease with mild to moderate aortic valve stenosis as defined by Doppler echocardiography results: Aortic Valve mean pressure gradient between 10-30 mmHg and Aortic Valve Area ≥ 1.2 and ≤ 2.0 cm2 on TTE within 2 weeks prior to randomization and Cardiac Compute Tomography (CT) test results: aortic valve calcium score (Agatston score) ≥ 200 AU at baseline cardiac CT within 1 month prior to randomization
Subject provides written informed consent prior to initiation of any study procedures.
Subject understands and agrees to comply with planned study procedures.

Exclusion Criteria:

Subject has concomitant moderate or severe mitral or tricuspid valve disease.
Subject has left ventricular ejection fraction < 50%.
Subject previous history of aortic valve surgery, pancreatitis, malignant tumor, drug or alcohol abuse.
Subjects whose alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 times the upper limit of normal range.
Subjects who cannot undergo Cardiac CT.
Pregnant or lactating women.
Consideration by the investigator, for safety reasons, that the subject is an unsuitable candidate to receive study treatment.