Dapagliflozin in patients with Right Heart Failure (Dapa-RHF)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsmedizin Goettingen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

29 Apr 2024 → ongoing

Decision date (initial)

2024-08-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515044-23-01

EudraCT number

2022-000420-38

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To demonstrate that dapagliflozin on top of standard of care is superior in reducing the primary outcome in patients with chronic right heart failure compared to standard of care plus placebo.

Conditions and MedDRA coding

Chronic right heart failure

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. The Patient is willing and able to participate and provide written informed consent
2. Age ≥ 18 years and < 90 years
3. Presence of RHF defined as (criteria a-c must all be fulfilled): a) Reduced right ventricular systolic function or RV strain defined as at least one of the following  tricuspid annular plane systolic excursion (TAPSE) <16 mm  RV fractional area change (FAC) <35%  Systolic pulmonary artery pressure (PAP sys) ≥35 mmHg combined with an extended inferior vena cava (>2,1 cm) with reduced collapsibility (<50%) during sniff inspiration assessed in echocardiography b) N-terminal pro-BNP (NT-proBNP) >125 pg/ml c) Clinical signs of right cardiac congestion (edema, and / or extended inferior vena cava (>2,1 cm) with reduced collapsibility (<50%) during sniff inspiration assessed in echocardiography and / or pleural effusion on sonography and / or chest radiograph) or need for diuretic therapy to prevent signs of congestion
4. For women of childbearing potential* (until 1 year after menopause): a) Negative pregnancy test AND b) Use of highly effective methods of contraception during treatment plus 5 days after the end of study drug administration

Exclusion criteria 21

1. Heart failure with reduced left ventricular (LV) ejection fraction (LVEF <40%)
2. Pulmonary arterial hypertension (PAH, PH Group I)
3. Acute (within 30 days) pulmonary embolism
4. Acute (within 30 days) right ventricular myocardial infarction
5. Current medication with any SGLT2 inhibitor
6. Chronic kidney disease (CKD) or acute kidney injury with eGFR < 25 ml/min/1,73 m², or end-stage renal failure with the need for chronic dialysis treatment
7. Systolic blood pressure (SBP) <90 mmHg at screening visit confirmed on 2 consecutive measurements
8. Any contraindication for cardiac magnetic resonance imaging (MRI)
9. Known intolerance or hypersensitivity to dapagliflozin
10. Known contraindication for the treatment with dapagfliflozin
11. Type 1 diabetes mellitus
12. Incapacity to understand the nature, significance and implications of the clinical trial and / or to provide written informed consent
13. Known active alcohol and / or drug abuse
14. Current participation in another interventional trial
15. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca personnel and/or personnel at the study site)
16. Pregnancy or lactating women
17. Body mass index >50 kg/m2
18. Known acute or chronic liver disease with clinical signs of severe impairment of liver function (e.g., ascites, oesophageal varices, coagulopathy)
19. Hepatic impairment defined as aspartate transaminase [AST] or alanine transaminase [ALT] >3x the upper limit of normal [ULN]; or total bilirubin >2x ULN at time of enrolment)
20. Previous cardiac transplantation or implantation of a ventricular assistance device (VAD) or similar device, or implantation expected after randomization
21. Active symptomatic infection (e. g. with body temperature ≥38°C) requiring anti-infective treatment (based on investigator's clinical judgement)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in serum NT-proBNP level from baseline to end of treatment (Delta-NTproBNP)

Secondary endpoints 4

1. Change in quality of life assessed by overall summary score of the Kansas City Cardiomyopathy Questionnaire (KCCQ) (a specific HF patient reported outcome questionnaire) from baseline to end of treatment
2. Change in RV ejection fraction (RV EF) [%] assessed in cardiac MRI from baseline to end of treatment
3. Change in exercise capacity assessed by the 6 min walking distance [meters] from baseline to end of treatment
4. Change in NYHA (New York Heart Association) class from baseline to end of treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsmedizin Goettingen

Sponsor organisation

Universitaetsmedizin Goettingen

Address

Robert-Koch-Strasse 40, Weende Weende

City

Goettingen

Postcode

37075

Country

Germany

Scientific contact point

Organisation

Universitaetsmedizin Goettingen

Contact name

Annika Wille

Public contact point

Organisation

Universitaetsmedizin Goettingen

Contact name

Annika Wille

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 3 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications