A clinical trial to determine if the test drug (Dapagliflozin) is better that placebo (Dummy drug) when used along with the standard therapy in patients with chronic heart failure in reducing incidence of worsening of this condition

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2017/08/009207
• Date of registration: 01-08-2017
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A clinical trial to determine if the test drug (Dapagliflozin) is better that placebo (Dummy drug) when used along with the standard therapy in patients with chronic heart failure in reducing incidence of worsening of this condition
• Scientific title: Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients with Chronic Heart Failure with Reduced Ejection Fraction
• Date of first enrolment: 14-08-2017
• Target sample size: 7000
• Recruitment status: Closed to Recruitment of Participants
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19044
• Study type: Interventional
• Study design: Randomized, Parallel Group, Placebo Controlled Trial; Method of generating randomization sequence:Stratified block randomization Method of allocation concealment:Centralized Blinding and masking:Double Blind Double Dummy
• Phase: Phase 3

Countries of recruitment

Argentina, Brazil, Bulgaria, Canada, China, Czech Republic, Denmark, Germany, Hungary, India, Japan, Netherlands, Poland, Romania, Russian Federation, Slovakia, Sweden, Taiwan, United Kingdom, United States of America, Viet Nam

Contacts

• Name: Mr Tapankumar M Shah
• Affiliation: AstraZeneca Pharma India Limited

• Name: Mr Tapankumar M Shah
• Affiliation: AstraZeneca Pharma India Limited

Key inclusion & exclusion criteria

Inclusion criteria: 1. Provision of signed informed consent prior to any study specific procedures

2. Male or female, aged >=18 years at the time of consent

3. Established documented diagnosis of symptomatic HFrEF (NYHA functional class II-IV), which has been present for at least 2 months and is optimally treated with pharmacological and/or device therapy, as indicated

4. LVEF<=40% (echocardiogram, radionuclide ventriculogram, contrast angiography or cardiac MRI) within the last 12 months prior to enrolment (Visit 1)

5. NT-proBNP >600 pg/ml (or if hospitalized for heart failure within the previous 12 months, NT-proBNP >=400 pg/ml) at enrolment (visit 1)
Exclusion criteria: 1. Receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor

2. Type 1 diabetes mellitus (T1D)

3. Symptomatic hypotension or systolic BP <95 mmHg on 2 consecutive measurements

4. Current acute decompensated HF or hospitalization due to decompensated HF <4 weeks prior to enrolment

5. MI, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment

6. Coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or valvular repair/replacement within 12 weeks prior to enrolment or planned to undergo any of these operations after randomization

7. Implantation of a cardiac CRT within 12 weeks prior to enrolment or intent to implant a CRT device

8. Women of child-bearing potential (ie, those who are not chemically or surgically sterilised or who are not post-menopausal) who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator OR women who have a positive pregnancy test at enrolment or randomization OR women who are breast-feeding



Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Men and women â?¥18 years of age with an established diagnosis of HFrEF for â?¥ 2 months and at a high risk of CV death or HF events Health Condition 2: I258- Other forms of chronic ischemic heart disease

Intervention(s)

Intervention1: Dapagliflozin: Dapagliflozin/Placebo Frequency: Once in a day Route of administration: Oral Total duration of therapy: 24 months
Control Intervention1: Placebo: Matching placebo for Dapagliflozin

Primary Outcome(s)

To determine, as a superiority assessment, whether treatment with dapagliflozin 10 mg, when added to standard of care, will reduce the incidence of the composite endpoint of CV death or hospitalization for heart failure or equivalent HF event (hereafter referred to as Heart Failure Event)Timepoint: Time to the first occurrence of any of the components of this composite:

1. CV death

2. Hospitalisation for heart failure

3. An urgent heart failure visit

Secondary Outcome(s)

To compare the effect of dapagliflozin versus placebo on total number of recurrent HF hospitalizations and CV death.Timepoint: Total number of recurrent HF hospitalizations and CV death.

To compare the effect of dapagliflozin versus placebo on CV death or hospitalization for HFTimepoint: Time to the first occurrence of any of the components of this composite:

1. CV death

2. Hospitalization for HF

To compare the effect of treatment with dapagliflozin versus placebo on the KCCQ

clinical summary score for HF symptoms and physical limitations.Timepoint: Change from baseline measured at 8 months in the overall summary score of the KCCQ, a specific HF patient reported outcome questionnaire.

To determine if dapagliflozin compared with

placebo reduces the incidence of a worsening

renal function composite outcomeTimepoint: Time to the first occurrence of any of the components of this composite:

1. â?¥50% sustained decline in eGFR

2. Reaching End Stage Renal Disease

- Sustained eGFR less than 15 ml/min/1.73m2 or

- Chronic dialysis treatment or

- Receiving a renal transplant

3. Renal death

Secondary ID(s)

Protocol No: D1699C00001 Version 1, Dated 26 OCT 2016

Source(s) of Monetary Support

AstraZeneca AB (Study Sponsor company) 151 85 Sodertalje, Sweden

Ethics review

Status: Approved
Approval date: 27/02/2017
Contact:

Ethics Committee, G.S.V.M Medical College

Status: Approved
Approval date: 28/03/2017
Contact:

Ethics Committee, KLE University

Status: Approved
Approval date: 03/04/2017
Contact:

Ethics Committee of Care Institute of Medical Science

Status: Approved
Approval date: 03/04/2017
Contact:

IPGME&R Research Oversight Committee

Status: Approved
Approval date: 05/04/2017
Contact:

Care Hospital, Nagpur, Ethics Committee

Status: Approved
Approval date: 10/04/2017
Contact:

KEM Hospital Research Centre, Ethics Committee

Status: Approved
Approval date: 24/04/2017
Contact:

Institutional Ethics Committee, H M Patel Centre for Medical Care & Education

Status: Approved
Approval date: 26/04/2017
Contact:

Institutional Ethics Committee, Dept. of Pharmacology, Govt. Medical College, Nagpur

Status: Approved
Approval date: 28/04/2017
Contact:

Artemis Health Sciences Institutional Ethics Committee

Status: Approved
Approval date: 26/06/2017
Contact:

Ethics Committee MGM Medical College

Status: Approved
Approval date: 10/07/2017
Contact:

Gujrat Methodist Church Cardiothoracic & Vascular Research Society Institutional Ethics Committee

Status: Approved
Approval date: 13/07/2017
Contact:

Institutional Ethics Committee, Noble Hospital Pvt. Ltd.

Status: Approved
Approval date: 17/07/2017
Contact:

The JMSHF and BMRC Institutional Ethics Committee,

Status: Approved
Approval date: 22/07/2017
Contact:

Rajarajeshwari Medical College and Hospital, Institutional Ethics Committee

Status: Approved
Approval date: 08/08/2017
Contact:

Ethics Committee, Shree Narayana Institute of Medical Sciences

Status: Approved
Approval date: 02/12/2017
Contact:

Institutional Ethics Committee of BJ Govt. Medical College and Sassoon Government Hospital

Status: Approved
Approval date: 02/12/2017
Contact:

Institutional Ethics Committee, Maulana Azad Medical College and Associated Hospitals

Status: Approved
Approval date: 14/12/2017
Contact:

Medanta Institutional Ethics Committee