Effect of Dapagliflozin Plus Low Dose Pioglitazone on Hospitalization Rate in Patients With HF and HFpEF

January 4, 2019 updated by: Hamad Medical Corporation

Effect of Combination Therapy With Dapagliflozin Plus Low Dose Pioglitazone on Hospitalization Rate in Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

The prevalence of type 2 diabetes mellitus (T2DM) in Qatar and nations worldwide has increased in recent decades into epidemic proportions. Cardiovascular (CVD) disease is the leading cause of death in T2DM patients. Approximately 80% of T2DM patients will die because of CV cause. Congestive heart failure (CHF) is a major cause of CV death in T2DM, and it also is responsible for significant morbidity and health care expenditure due to high rate of hospitalization for heart failure.

Study Overview

Status

Unknown

Conditions

Detailed Description

Community based studies have demonstrated similar prevalence of HF with reduced ejection fraction (HFpEF) and HF with reduced LV function (HFrEF) in patients hospitalized for CHF. Moreover, the prevalence of HFrEF is declining over the past two decades, whereas that of HFpEF is progressively increasing. Progressive increase in obesity and T2DM prevalence is likely among the principal factors responsible for the steady increase in HFpEF prevalence.

The aims of the present study are to examine whether therapies that correct the myocardial metabolic abnormalities present in subjects with T2DM and diastolic dysfunction improve myocardial diastolic dysfunction and reduce the rate of hospitalizations in patients with HFpEF

The primary objective of the study is to examine the effect of combination therapy with pioglitazone (15 mg) plus dapagliflozin (10 mg) versus placebo on hospitalization for heart failure in patients with HFpEF.

Eligible subjects, who consent for participating in the study, will be seen by the study coordinator. Medical history and physical examination will be performed. Each subject will receive the following measurements:

Medical history and physical examination including weight, height, waist, blood pressure and pulse.

Blood tests:

Screening: CBC, Blood chemistry, fasting plasma glucose concentration, HbA1c, renal and liver function, lipid profile, TSH, serum iron, iron biding capacity and ferritin.

Plasma metabolites: ketone, lactate, bicarbonate, venous PH and plasma free fatty acid.

Hormones: insulin, C-peptide, glucagon, NT proBNP, angiotensin II, plasma renin activity, and aldosterone.

Inflammatory markers: adiponectin, hsCRP, IL-2, IL-6 and IL-12, F2-isoprostane, oxidized LDL.

Vascular Measurements: Measurement of pulse wave velocity, and central aortic pulse pressure, with sphygmocor.

Measurement of total body fat mass with Bioimpedence. Echocardiography

Patients will be consented on the day of discharge or during the outpatient visit in the Cardiology Clinic. Consented patients will be referred to the CRC within one week to perform the echocardiography and vascular measurements. Patients will be asked to come to CRC after overnight fast and blood samples will be drawn for the above mentioned blood tests, after which echocardiography and vascular measurements will be performed.

Randomization and Intervention:

After completing the baseline studies, patients will be randomized into two groups to receive in a double blind fashion:

Group 1: combination of pioglitazone plus dapagliflozin, or Group 2: Placebo (Beta blockers, ACEI, ARB, and aldosterone )

Patients in both groups will be matched for age, gender, BMI, HbA1c, systolic BP and LVEF. Randomization will be made by the pharmacist at the Heart Hospital and the randomization code will be maintained at the hospital pharmacy. Patients will be randomized in blocks of 4 while the group means are matched for the above parameters

Study Type

Interventional

Enrollment (Anticipated)

648

Phase

  • Phase 3

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

      • Doha, Qatar, 3050
        • Heart Hospital, Hamad Medical Coorporation

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

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Diagnosis of type 2 diabetes according to the ADA criteria.
  2. Drug naïve or on stable dose of antidiabetic therapy (oral agents and/or insulin) for 3 months preceding recruitment.
  3. Hospitalized for HFpEF (defined as hospitalization require intravenous diuresis) in the 6 months preceding recruitment.
  4. eGFR >60 ml/min
  5. LVEF >50%
  6. Presence of LV diastolic dysfunction in echocardiography

We have limited the inclusion criteria in the present study to T2DM patients with HFpEF and evidence of diastolic dysfunction by echocardiography in order to select a homogenous group of HFpEF patients with similar etiology, likely "metabolic HFpEF". We believe that this subgroup of HFpEF will benefit most from treatment with low dose pioglitazone (15 mg) plus dapagliflozin (10 mg).

Exclusion Criteria:

  1. Treatment with pioglitazone or SGLT2 inhibitor in the 3 months prior to recruitment.
  2. eGFR < 60 ml/min
  3. LVEF <50%;
  4. Valvular heart disease, ASD, VSD
  5. Chronic lung disease
  6. Cancer
  7. diabetes mellitus type 1
  8. patients with acute coronary syndrome, stroke or transient ischemic attack in the preceding 6 months
  9. pregnancy or lactation period

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: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pioglitazone Plus dapaglifliozin
Pioglitazone 15mg and dapaglifliozin 10mg together in T2DM patients having HF and HFpEF conditions
Pioglitazone Plus dapaglifliozin
Placebo Comparator: Placebo
Beta blockers, ACEI, ARB, and aldosterone
(Beta blockers, ACEI, ARB, and aldosterone )

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to first hospitalization for heart failure after starting intervention
Time Frame: 3 years
Hospitalization for heart failure will be defined as a hospitalization >24 hours requiring intravenous diuretic infusion.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of all cause mortality
Time Frame: 3 years
Composite outcome comprised of total mortality, incidence of acute coronary syndrome and non fatal CVA
3 years

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Nidal Asaad, MD, Heart Hospital, HMC, Doha, Qatar

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Anticipated)

March 1, 2019

Primary Completion (Anticipated)

September 1, 2021

Study Completion (Anticipated)

December 1, 2021

Study Registration Dates

First Submitted

August 1, 2018

First Submitted That Met QC Criteria

January 4, 2019

First Posted (Actual)

January 7, 2019

Study Record Updates

Last Update Posted (Actual)

January 7, 2019

Last Update Submitted That Met QC Criteria

January 4, 2019

Last Verified

July 1, 2018

More Information

Terms related to this study

Other Study ID Numbers

  • IRGC-04-SI-17-116

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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