Effects of Pioglitazone in Calcific Aortic Valve Disease

Study Overview
=================
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.

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.

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

Conditions
-----------------
Calcification of Aortic Valve, Aortic Valve Stenosis

Intervention / Treatment
-----------------
* Drug: Drug: Pioglitazone Oral Tablet
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 35 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug group<br>Dietary Supplement: Pioglitazone 30 mg by mouth daily | Drug: Drug: Pioglitazone Oral Tablet<br>* Dietary Supplement: Pioglitazone 30 mg by mouth daily<br>|
| Placebo Comparator: Control group<br>Dietary Supplement: Placebo | Dietary Supplement: Placebo<br>* Dietary: Supplement: Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | overall survival (OS) | 3 years | 

Secondary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Calcification of Aortic Valve, Aortic Valve Stenosis, Pioglitazone