Overview
Sponsor-declared trial summary
aortic stenosis patients with high fibrotic burden
The aim of the study is to evaluate the effect of antifibrotic therapy on regression of myocardial fibrosis after TAVI in patients with baseline high fibrotic burden. Therefore, patients will be treated with Spironolactone in addition to standard of care, Spioronolactone + Dihydralazine in addition to standard of care …
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
- 28 Feb 2022 → 24 Feb 2026
- Decision date (initial)
- 2024-07-26
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-510869-42-00
- EudraCT number
- 2019-004244-29
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Efficacy
The aim of the study is to evaluate the effect of antifibrotic therapy on regression of myocardial fibrosis after TAVI in patients with baseline high fibrotic burden. Therefore, patients will be treated with Spironolactone in addition to standard of care, Spioronolactone + Dihydralazine in addition to standard of care or according to standard of care alone without any study medication. First, differences between patients in the control arm and patients randomized to anti-fibrotic therapy will be analyzed. The second analysis will determine, whether dihydralazine medication in addition to spironolactone is able to increase a potential antifibrotic effect. Myocardial fibrosis will be assessed by cardiac magnetic resonance imaging (CMR) before TAVI and 1 year after. Quantification of potentially irreversible replacement fibrosis will be carried out by late gadolinium enhancement (LGE), and quantification of the potentially reversible diffuse interstitial fibrosis will be performed by measurement of the extracellular volume fraction (ECV), thereby deriving matrix volume and cell volume.
Conditions and MedDRA coding
aortic stenosis patients with high fibrotic burden
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.1 | PT | 10002906 | Aortic stenosis | 100000004866 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Male, female age ≥ 60
- Diagnosis of severe symptomatic aortic stenosis
- Transcatheter aortic valve implantation therapy (TAVI) scheduled
- Written informed consent
Exclusion criteria 17
- Pre-existing dilative or ischemic heart disease with EF<35% and guideline indication for spironolactone
- Patient on current medication with spironolactone, eplerenone, or dihydralazine
- Presence of coexistent myocardial pathology such as cardiac amyloidosis, hypertrophic cardiomyopathy, or myocarditis
- Presence of coexistent severe aortic regurgitation or severe mitral stenosis
- Previous surgical valve replacement or repair
- Pacemaker or ICD implanted
- Renal impairment (serum creatinine > 1,8 mg/dl and/ or GFR < 30 ml/min/1,73 m² BSA)
- Significant hypotension (blood pressure < 90 mm Hg systolic and/or < 50 mm Hg diastolic
- Serum potassium > 5,1 mmol/l
- Contraindications for Spironolactone (anuria, acute renal failure, serum creatinine > 1.8 mg/dl, hyperkalemia, pregnancy)
- Contraindications for Dihydralazine (known allergy or hypersensitivity, systemic lupus erythematodes, adrenocortical disorders)
- Known active malignant disease with life expectancy < 1 year
- Women with child-bearing potential
- Simultaneous participation (including a waiting period of 4 weeks) in other interventional clinical trials
- Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial
- Person who is in a relationship of dependence/employment with the sponsor or the investigator
- Known planned operations or catheter-based interventions (e.g. PCI, transcatheter edge-to-edge mitral or tricuspid valve repair) during 3 months after study inclusion; the performance of e.g. PCI immediately before study enrolment and before TAVI is possible
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Differences between treatment groups in reduction of extracellular volume (ECV)- derived matrix volume (measured by CMR) after 12 months
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
Aldactone® 25, 25 mg überzogene Tabletten
PRD918036 · Product
- Active substance
- Spironolactone
- Pharmaceutical form
- COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 9125 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- C03DA01 — SPIRONOLACTONE
- Marketing authorisation
- 6618622.00.00
- MA holder
- ESTEVE PHARMACEUTICALS GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD387556 · Product
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 50 mg milligram(s)
- Max total dose
- 18250 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- C02DB01 — DIHYDRALAZINE
- Marketing authorisation
- 5036.00.00
- MA holder
- TEOFARMA S.R.L.
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
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
- Florian Walker
Public contact point
- Organisation
- Universitaetsmedizin Goettingen
- Contact name
- Florian Walker
Locations
1 EU/EEA country · 15 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Germany | Ended | 150 | 15 |
| 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 |
|---|---|---|---|---|---|
| Germany | 2022-02-28 | 2026-02-24 | 2022-03-21 | 2024-07-24 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 6 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Reduce-MFA_CTP_for pub | 9 |
| Recruitment arrangements (for publication) | Reduce-MFA_Document not applicable acc to Clinical Trials Directive EC No 200120EC | 1 |
| Subject information and informed consent form (for publication) | L1_Reduce-MFA_PatInfo_for Pub | 4.2 |
| Subject information and informed consent form (for publication) | L1_Reduce-MFA_PIC_Biomaterialsammlung_for Pub | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G_FI_Aldactone_25_Spironolacton_Feb_2022 | 2.0 |
| Summary of Product Characteristics (SmPC) (for publication) | G_FI_Nepresol_25_Dihydralazin _ Juni_2015 | 1 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-09 | Germany | Acceptable 2024-07-19
|
2024-07-26 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-09-16 | Germany | Acceptable 2024-11-07
|
2024-11-07 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-06-27 | Germany | Acceptable 2024-11-07
|
2025-06-27 |