DAPAgliflozin for Renal Protection in Heart Transplant Recipients

NCT05321706 | Recruiting Phase 3

• 1 other identifier: 2021-003175-34
• Study Type: interventional
• Target: 430
• Locations: 3 countries
• Sites: 6

Brief Summary

Kidney failure is common in heart transplant recipients and is a major cause of morbidity and mortality. Sodium-glucose transporter 2 (SGLT2) inhibitors were developed as antidiabetics but were subsequently shown to reduce the incidence of adverse cardiovascular outcomes and protect renal function in non-diabetics as well as diabetics. However, SGLT2 inhibitors have not been tested in clinical trials in heart transplant recipients. The DAPARHT trial is designed to assess the effect of the SGLT2 inhibitor dapagliflozin to prevent deteriorating renal function in heart transplant recipients. Secondary objectives are to assess the impact of treatment on i) weight, ii) glucose homeostasis, iii) proteinuria, iv) the number of rejections, and (v) safety and tolerability. As exploratory outcomes, the investigators will assess the effect of treatment on renal outcomes, clinical events (death, myocardial infarction, cerebral stroke, cancer, and end-stage renal disease), cardiac function, quality of life, and new-onset diabetes.

Conditions

Heart Transplant Failure; Kidney Failure

Keywords

Renal protection; Heart transplant; Dapagliflozin

Outcome Measures

Primary Outcomes (1)

• The chronic slope of the eGFR

  The primary endpoint will be the slope of the eGFR from 2 weeks to end-of-treatment (12 months), calculated as the difference in eGFR from two weeks to 12 months after start of the intervention.

  From 2 weeks to end-of-treatment (12 months)

Secondary Outcomes (3)

• Body weight

  From 2 weeks to end-of-treatment (12 months)

• Glycosylated hemoglobin (HbA1c)

  From 2 weeks to end-of-treatment (12 months)

• Proteinuria

  From 2 weeks to end-of-treatment (12 months)

Study Arms (2)

Dapagliflozin

ACTIVE COMPARATOR

Participants will be randomized in a 1:1 fashion to receive 10 mg of oral dapagliflozin (tablet) once daily for one year.

Drug: Dapagliflozin 10 mg

Placebo

PLACEBO COMPARATOR

Participants will be randomized in a 1:1 fashion to receive a matching tablet once daily for one year.

Drug: Placebo

Interventions

Dapagliflozin 10 mg DRUG

Participants will be randomized in a 1:1 fashion to receive 10 mg of oral dapagliflozin

Also known as: Farxiga

Dapagliflozin

Placebo DRUG

Participants will be randomized in a 1:1 fashion to receive a matching placebo once daily for one year.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Heart transplant recipient ≥ 1 year after heart transplant.
• Age ≥ 18 years

You may not qualify if:

• Contraindications to study medication.
• Estimated GFR \< 25 ml/min/m2
• Type I diabetes
• Severe liver failure (Child-Pugh's score C)
• Life expectancy reduced to \< 2 years as judged by the investigator
• Unresolved malignant disease
• Failure to obtain written informed consent
• SGL2 inhibitor treatment over the last month
• Pregnancy
• Breast-feeding
• Woman of child-bearing potential who is not willing to use a highly effective method of birth control

Sponsors & Collaborators

• Oslo University Hospital: lead
• Erasmus Medical Center: collaborator
• Skane University Hospital: collaborator
• Aarhus University Hospital: collaborator
• Karolinska University Hospital: collaborator
• Sahlgrenska University Hospital: collaborator

Study Sites (6)

University Medical Center Groningen

Groningen, Netherlands

RECRUITING

Erasmus Medical Center

Rotterdam, Netherlands

RECRUITING

Oslo University Hospital, Rikshospitalet

Oslo, Oslo County, 0372, Norway

RECRUITING

Sahlgrenska University Hospital

Gothenburg, SE-41345, Sweden

NOT YET RECRUITING

Skane University Hospital

Lund, 22185, Sweden

NOT YET RECRUITING

Karolinska University Hospital

Stockholm, Sweden

NOT YET RECRUITING

Related Publications (2)

• Holmen S, Manintveld O, Damman K, Braun O, Lofman IH, Szymanski M, Ravnestad H, Gude E, Bjorkelund E, Andreassen AK, Gullestad L, Broch K. DAPAgliflozin for renal protection in heart transplant recipients. Rationale and design of the randomized controlled DAPARHT trial. Am Heart J. 2026 Jan;291:128-135. doi: 10.1016/j.ahj.2025.08.010. Epub 2025 Aug 19.

  PMID: 40840822 DERIVED

• Garcia-Cosio Carmena MD, Farrero M, Blasco Peiro MT, Crespo M, Delgado Jimenez J, Diaz Molina B, Fernandez Rivera C, Garrido Bravo IP, Lopez Jimenez V, Melilli E, Mirabet Perez S, Perez Tamajon ML, Rangel Sousa D, Rodrigo E, Cruzado JM, Hernandez Marrero D; Spanish Society of Transplantation, the Spanish Society of Nephrology, and the Spanish Society of Cardiology (SET-SEC-SEN). Management of Kidney Disease in Heart Transplant Patients: A National Delphi Survey-based Consensus Expert Paper. Transplantation. 2025 Sep 1;109(9):e431-e445. doi: 10.1097/TP.0000000000005302. Epub 2025 Feb 7.

  PMID: 39928546 DERIVED

MeSH Terms

Conditions

Renal Insufficiency

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Olivier Manintveld, MD, PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

• Oscar Braun, MD, PhD

  Skane University Hospital

  PRINCIPAL INVESTIGATOR

• Ida H Löfman, MD, PhD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

• Kevin Damman, MD, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kaspar Broch, MD, PhD

CONTACT

+4792091824; sbbrok@ous-hf.no

Lars Gullestad, MD, PhD

CONTACT

+4797644772; lars.gullestad@medisin.uio.no

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: One year's blinded treatment + two years' open-label extension. The primary endpoint of the blinded phase of the trial is the difference in the slope from 2 weeks to 12 months in the eGFR. The major endpoint of the open-label phase is the baseline-adjusted eGFR measured 1 months after the end of treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD, PhD

Model Details: The DAPARHT trial is a randomised, controlled, double blind, parallel group trial with an open-label extension phase. The primary endpoint is the slope of the eGFR measured from 2 weeks after randomisation and start of treatment to 12 months after start of treatment. The trial subjects immediately continue into the open-label phase. In this phase, patients assigned to dapagliflozin continue treatment for another 24 months. The primary endpoint of the open-label extension is the baseline-adjusted eGFR measured one month after the end of treatment, 37 months after randomisation.

Study Record Dates

• First Submitted: March 22, 2022
• First Posted: April 11, 2022
• Study Start: June 8, 2022
• Primary Completion: April 30, 2026
• Study Completion (Estimated): May 31, 2028
• Last Updated: October 3, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2); SE (3); NO (1)