Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruitment ended
Participants planned
270
Countries
3
Sites
6
Heart transplant
The main goal of the DAPARHT trial is to evaluate the effect of dapagliflozin on renal function in cardiac allograft recipients
Key facts
- Sponsor
- Oslo University Hospital HF
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 26 Apr 2022 → ongoing
- Decision date (initial)
- 2023-10-17
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Oslo University Hospital · Norwegian Health Association · AstraZeneca · Stiftelsen Kardimmun
External identifiers
- EU CT number
- 2023-506486-60-01
- EudraCT number
- 2021-003175-34
- ClinicalTrials.gov
- NCT05321706
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
The main goal of the DAPARHT trial is to evaluate the effect of dapagliflozin on renal function in cardiac allograft recipients
Secondary objectives 5
- Assess the effect of dapagliflozin on weight
- Assess the effect of dapagliflozin on proteinuria in patients with an albumin/creatinine ratio of 30 g/mg
- Assess the effect of dapagliflozin on HbA1c in the subset of patients who have type two diabetes
- Safety
- The main goals of the open-label extension phase will be to evaluate the effect of oral dapagliflozin on renal function, clinical events, and tolerability
Conditions and MedDRA coding
Heart transplant
Study design 2 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Blinded treatment phase The blinded treatment phase lasts for 12 months. The primary endpoint is calculated based on the study results in the blinded treatment phase. After eligible participants have provided infiormed consent, he or she will be randomised to treatment with oral dapagliflozin or matching placebo. The randomisation process will be performed online via the comercially available electronic case report form (eCRF) system called VieDoc(R). The investigational drug, oral dapagliflozin 10 mg or matching placebo, is taken once daily for the duration of the blinded treatmnet phase (12 months). There will be no dose titration. At the end of the blinded treatment phase, the efficacy measurements will be performed, stored and locked, and all adverse events will be recorded before study drug allocation is revealed in VieDoc, and the patient is invited to enter the open-label phase
|
Randomised Controlled | Double | [{"id":119844,"code":2,"name":"Investigator"},{"id":119847,"code":4,"name":"Analyst"},{"id":119843,"code":1,"name":"Subject"},{"id":119845,"code":5,"name":"Carer"},{"id":119846,"code":3,"name":"Monitor"}] | |
| 2 | Open label phase The open-label extension phase begins at the end of the first year of (blinded) treatment and is scheduled to last for two years (until three years after randomisation). The patients will transfer from the blined treatment phase only after data lock (in the eCRF) and continue open label treatment if originally randomised to active treatment or receive no study drug if originally allocated to placebo
|
Not Applicable | None |
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2024-510830-42-00 | IMPD-Q-only application | AstraZeneca AB |
| 2023-506486-60-00 | DAPARHT: DAPAgliflozin for Renal protection in Heart Transplant recipients | Oslo University Hospital HF |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Heart transplant recipient for ≥ 1 year
- Age ≥ 18 years
- Informed consent obtained and documented according to Good Clinical Practice (GCP), and national/regional regulations
- Estimated glomerular filtration rate ≥ 25 ml/min/1.73 m2 as assessed by the MDRD formula
- The subject is, in the opinion of the Investigator, clinically suitable for randomisation to dapagliflozin/placebo
Exclusion criteria 11
- Contraindications to study medication
- Estimated GFR < 25 ml/min/m2
- Type 1 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 four weeks prior to randomisation
- Pregnancy
- Breastfeeding
- Female subject who has either (1) not used at least one highly effective method of birth control for at least 1 month prior to screening or (2) is not willing to use such a method during treatment and for an additional 15 weeks after the end of treatment, unless the subject is sterilised or postmenopausal
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- 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. The eGFR is calculated from serum creatinine using the Modification of Diet in Renal Disease (MDRD) formula
Secondary endpoints 5
- Baseline-adjusted body weight
- The change in the albumin / creatinine ratio in the urine from baseline to end-of-treatment in patients with a baseline ratio > 30 mg/g at baseline
- The change in the blood level of glycated haemoglobin (HbA1c) in patients with diabetes mellitus
- Change in body composition (exploratory endpoint)
- Biomarkers of renal damage (i.e. Cystatin-C, Lipocalin (NGAL), KIM-1, osteopontin) (exploratory endpoints)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SUB31650 · Substance
- Active substance
- Dapagliflozin
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
Placebo for dapagliflozin film-coated tablets 10 mg
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Oslo University Hospital HF
- Sponsor organisation
- Oslo University Hospital HF
- Address
- P. O. Box 4953
- City
- Oslo
- Postcode
- 0424
- Country
- Norway
Scientific contact point
- Organisation
- Oslo University Hospital HF
- Contact name
- Clinical trial unit
Public contact point
- Organisation
- Oslo University Hospital HF
- Contact name
- Clinical trial unit
Locations
3 EU/EEA countries · 6 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ongoing, recruitment ended | 70 | 3 |
| Norway | Ongoing, recruitment ended | 100 | 1 |
| Sweden | Ongoing, recruitment ended | 100 | 2 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2023-08-25 | 2023-10-19 | 2025-09-24 | ||
| Norway | 2022-04-26 | 2022-06-22 | 2025-09-24 | ||
| Sweden | 2024-10-01 | 2024-10-18 | 2025-09-24 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 5 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Recruitment arrangements (for publication) | K1_Recruitment_arrangements_NL | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment_arrangements_SE | 2 |
| Subject information and informed consent form (for publication) | L1_Informed consent form NL | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_SE_Lund | 1.4 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_SE_Stockholm | 1.4 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-09-08 | Norway | Acceptable 2023-10-16
|
2023-10-17 |
| 2 | SUBSTANTIAL MODIFICATION | SM-3 | 2024-02-07 | Norway | Acceptable 2024-04-22
|
2024-05-02 |
| 3 | SUBSEQUENT ADDITION OF MSC | APP-3 | 2024-06-28 | 2024-09-11 | ||
| 4 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-02-06 | Acceptable | 2025-02-28 | |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-04-08 | Norway | Acceptable | 2025-04-08 |