NCT02397421

Brief Summary

Patients with diabetes are at increased risk of developing heart failure (HF) which can lead to increased shortness of breath, reduced ability to exercise and in some cases premature death as the heart becomes less efficient at pumping blood around the body. However the treatment options for such patients remain limited. This study will test the safety and benefits of using a new class of drug, the SGLT2 Inhibitor (Dapagliflozin), in treating HF and diabetes. Participants will have a Magnetic Resonance Imaging (MRI) scan of the heart, to measure the efficiency and the extent of thickening of the heart muscle before they start on treatment of dapagliflozin, or placebo for one year. They will also do exercise testing on an exercise bike (if capable) and a walking test plus fill in some questionnaires on how their heart failure affects their quality of life. Participants will then continue as normal with currently prescribed medication for their diabetes and heart failure. After a year the tests will be repeated to determine if patients receiving Dapagliflozin benefited more than those who weren't on the drug. This study is funded by the European Foundation for the Study of Diabetes (EFSD)

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
56

participants targeted

Target at P25-P50 for phase_4 heart-failure

Timeline
Completed

Started Mar 2015

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2015

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

March 12, 2015

Completed
13 days until next milestone

First Posted

Study publicly available on registry

March 25, 2015

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2017

Completed
Last Updated

July 31, 2018

Status Verified

July 1, 2018

Enrollment Period

2.4 years

First QC Date

March 12, 2015

Last Update Submit

July 29, 2018

Conditions

Heart FailureDiabetes

Keywords

Heart failureDiabetesLeft ventricular remodellingSGLT-2 inhibitors

Outcome Measures

Primary Outcomes (1)

  • Change in LV end systolic volume (absolute value and indexed for BSA) or LV end diastolic volume (absolute value and indexed for BSA)

    Cardiac MRI will be performed to determine the change in end systolic and diastolic volumes between both groups of patients

    1 year

Secondary Outcomes (10)

  • Change in LV mass, LV ejection fraction, RV end diastolic volume, RV end systolic volume, RV ejection fraction, atrial dimensions and volumes, and LV remodelling index (LV mass / LVEDV)

    1 year

  • Fluid status (Bioelectrical Impedence Analysis (BIA)

    1 year

  • Objective functional capacity (6 Minute Walk Test (6MWT)

    1 year

  • Exercise capacity (Cardio-pulmonary Exercise Testing (CPET)

    1 year

  • Quality of life (Minnesota Living with Heart Failure and SF-36 questionnaire)

    1 year

  • +5 more secondary outcomes

Study Arms (2)

Treatment

ACTIVE COMPARATOR

Dapagliflozin 10mg once daily

Drug: Dapagliflozin

Control

PLACEBO COMPARATOR

Capsules containing microcrystalline cellulose Ph Eur overencapsulated in a hard gelatine capsule shell to match the active comparator

Drug: Placebo

Interventions

DapagliflozinDRUG

Sodium Glucose Linked Transporter Type 2 (SGLT-2) Inhibitor

Also known as: Forxiga
Treatment
PlaceboDRUG

Capsules containing microcrystalline cellulose Ph Eur overencapsulated in a hard gelatine capsule shell to match the active comparator

Control

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • were previously diagnosed with Type 2 Diabetes
  • are diagnosed with NYHA functional class I-III HF with prior echocardiographic evidence of Left Ventricular Systolic Dysfunction (LVSD) (At least mild LV systolic dysfunction on sonographer assessment or ejection fraction at 45% or less)
  • on furosemide 80mg daily or less, or equivalent loop diuretic
  • have stable HF symptoms for at least three months prior to consent
  • on stable therapy for HF for at least three months prior to consent
  • have not been hospitalised for HF for at least three months prior to consent

You may not qualify if:

  • severe hepatic disease
  • renal disease defined as Chronic Kidney Disease (CKD) class 3b or worse (i.e. estimated glomerular filtration rate (eGFR) / creatinine clearance CrCl \<45ml/min)
  • systolic BP \<95mmHg at screening visit
  • screening HbA1c \<6.0%
  • unable to walk to perform cardio pulmonary exercise testing or 6MWT
  • malignancy (receiving active treatment) or other life threatening diseases
  • pregnant or lactating women
  • any contraindication to MRI (e.g. claustrophobia, metal implants, penetrative eye injury or exposure to metal fragments in eye requiring medical attention)
  • patients who have participated in any other clinical trial of an investigational medicinal product within the previous 30 days
  • patients who are unable to give informed consent

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Ninewells Hospital and Medical School

Dundee, Angus, DD1 9SY, United Kingdom

Location

Related Publications (3)

  • Kanie T, Mizuno A, Takaoka Y, Suzuki T, Yoneoka D, Nishikawa Y, Tam WWS, Morze J, Rynkiewicz A, Xin Y, Wu O, Providencia R, Kwong JS. Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis. Cochrane Database Syst Rev. 2021 Oct 25;10(10):CD013650. doi: 10.1002/14651858.CD013650.pub2.

    PMID: 34693515DERIVED

  • Singh JSS, Mordi IR, Vickneson K, Fathi A, Donnan PT, Mohan M, Choy AMJ, Gandy S, George J, Khan F, Pearson ER, Houston JG, Struthers AD, Lang CC. Dapagliflozin Versus Placebo on Left Ventricular Remodeling in Patients With Diabetes and Heart Failure: The REFORM Trial. Diabetes Care. 2020 Jun;43(6):1356-1359. doi: 10.2337/dc19-2187. Epub 2020 Apr 3.

    PMID: 32245746DERIVED

  • Singh JS, Fathi A, Vickneson K, Mordi I, Mohan M, Houston JG, Pearson ER, Struthers AD, Lang CC. Research into the effect Of SGLT2 inhibition on left ventricular remodelling in patients with heart failure and diabetes mellitus (REFORM) trial rationale and design. Cardiovasc Diabetol. 2016 Jul 15;15:97. doi: 10.1186/s12933-016-0419-0.

    PMID: 27422625DERIVED

MeSH Terms

Conditions

Heart FailureDiabetes Mellitus

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular DiseasesGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Study Officials

  • Jagdeep Singh, MBBS

    University of Dundee

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Dr

Study Record Dates

First Submitted

March 12, 2015

First Posted

March 25, 2015

Study Start

March 1, 2015

Primary Completion

August 1, 2017

Study Completion

August 1, 2017

Last Updated

July 31, 2018

Record last verified: 2018-07

Locations

GB(1)