Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Authorised, recruitment pending
Participants planned
889
Countries
2
Sites
11
Diabetes mellitus Type 2
Superiority of high dose treatment with RAS-antagonists and beta-blockers compared to conventional therapy regarding the reduction of unplanned hospitalization or death due to a cardiac event in T2DM patients with a NT-proBNP > 125pg/ml. Co-primary objective Superiority of high dose treatment with RAS-antagonists and b…
Key facts
- Sponsor
- Medical University Of Vienna
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Cardiovascular Diseases [C14]
- Decision date (initial)
- 2025-02-17
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Medical University of Vienna
External identifiers
- EU CT number
- 2024-519051-28-01
- EudraCT number
- 2015-000239-34
- ClinicalTrials.gov
- NCT02817360
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Prophylaxis
Superiority of high dose treatment with RAS-antagonists and beta-blockers compared to conventional therapy regarding the reduction of unplanned hospitalization or death due to a cardiac event in T2DM patients with a NT-proBNP > 125pg/ml.
Co-primary objective
Superiority of high dose treatment with RAS-antagonists and beta-blockers compared to conventional therapy regarding the reduction of unplanned hospitalization or death due to a cardiac event in T2DM patients in the whole population.
Secondary objectives 1
- Dependency of treatment efficacy (reduction of unplanned hospitalization or death due to a cardiac event in T2DM patients) on the NT-proBNP concentration (interaction effect between NT-proBNP concentrations and treatment).
Conditions and MedDRA coding
Diabetes mellitus Type 2
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2024-519051-28-00 | NT-proBNP Selected PreventiOn of cardiac eveNts in a populaTion of dIabetic patients without A history of Cardiac disease; a prospective randomized trial | Medical University Of Vienna |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Type-2 diabetes mellitus for at least six months
- ≥18 years of age,men or female
- Written informed consent to participate in the study and ability to comply with all requirements
Exclusion criteria 18
- History of hypersensitivity to any of the drugs investigated as well as known or suspected contraindications to the study drugs or previous history of intolerance to high dose of RAAS-antagonists or beta-blocker in the absence of any other blood pressure lowering drugs
- Chronic infections or malignancies
- Systemic treatment with corticosteroids
- Renal replacement therapy
- Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum Follicle Stimulating Hormone (FSH) levels > 40mIU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy OR are using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation), hormonal contraception (implantable, patch, and oral), and double-barrier methods (if accepted by local regulatory authority and ethics committee). Reliable contraception should be maintained throughout the study and for 7 days after study drug discontinuation.
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive Human Chorionic Gonadotropin (hCG) laboratory test ( > 5mIU/ml).
- History of noncompliance to medical regimes and patients who are considered potentially unreliable
- Current double blind treatment in diabetic trials
- Participation in an investigational drug study at the time of enrollment or within the past 90 days.
- Patients already receiving a maximum dose of RAAS-antagonists or beta-blocker
- Creatinine>2.5mg/dl
- Symptomatic hypotension and/or systolic blood pressure(SBP) <100mmHg at visit 1
- Symptomatic bradycardia and/or heart rate (HR)<60bpm at visit 1
- Signs of cardiac disease in the electrocardiogram, such as atrial fibrillation, ST-T abnormalities, or a bundle branch block/ higher degree AV block
- Abnormal echocardiography, defined as low ejection fraction <50%; wall motion abnormalities suggesting coronary artery disease (CAD), significant valve dysfunction > grades I.
- Coronary artery disease, defined by a history of myocardial infarction, known coronary stenosis > 70% detected either by angiography or by CT-scan, significant defects in myocardial scintigraphy or positive stress-test echocardiography
- A disease other than diabetes lowering the patient’s life expectancy to less than two years.
- Exclusion criteria specific for Spain only
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Combined endpoint based on the first occurrence of cardiac death and cardiac hospitalization.
Secondary endpoints 6
- All cardiac hospitalization
- Heart failure hospitalization
- All cause hospitalization
- NT-proBNP
- Other predefined (see section plasma and serum biomarkers) biomarkers
- Health economic analysis (cost-effectiveness of intervention considering both life- years and quality of life adjusted life years)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 19
SCP1138921 · ATC
- Active substance
- Lisinopril Dihydrate
- Route of administration
- ORAL
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 40 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09AA03 — LISINOPRIL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP129020 · ATC
- Active substance
- Fosinopril Sodium
- Substance synonyms
- SODIUM (2S,4S)-4-CYCLOHEXYL-1-[2-[(2-METHYL-1-PROPANOYLOXY-PROPOXY)-(4-PHENYLBUTYL)PHOSPHORYL]ACETYL]PYRROLIDINE-2-CARBOXYLATE
- Route of administration
- ORAL
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 40 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09AA09 — FOSINOPRIL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP128193 · ATC
- Active substance
- Captopril
- Route of administration
- ORAL
- Max daily dose
- 150 mg milligram(s)
- Max total dose
- 150 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09AA01 — CAPTOPRIL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1083046 · ATC
- Active substance
- Losartan Potassium
- Route of administration
- ORAL
- Max daily dose
- 150 mg milligram(s)
- Max total dose
- 150 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09CA01 — LOSARTAN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP136325 · ATC
- Active substance
- Cilazapril
- Route of administration
- ORAL
- Max daily dose
- 5 mg milligram(s)
- Max total dose
- 5 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09AA08 — CILAZAPRIL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1159601 · ATC
- Active substance
- Metoprolol Succinate
- Substance synonyms
- BUTANEDIOIC ACID, 1-[4-(2-METHOXYETHYL)PHENOXY]-3-(PROPAN-2-YLAMINO)PROPAN-2-OL
- Route of administration
- ORAL
- Max daily dose
- 200 mg milligram(s)
- Max total dose
- 200 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C07AB02 — METOPROLOL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP103376519 · ATC
- Active substance
- Perindopril Tert-Butylamine
- Substance synonyms
- PERINDOPRIL ERBUMINE
- Route of administration
- ORAL
- Max daily dose
- 8 mg milligram(s)
- Max total dose
- 8 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09AA04 — PERINDOPRIL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
—
SCP196595 · ATC
- Route of administration
- ORAL
- Max daily dose
- 24 mg milligram(s)
- Max total dose
- 24 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09AA11 — SPIRAPRIL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP189600 · ATC
- Active substance
- Zofenopril Calcium
- Substance synonyms
- Zofenopril hemicalcium
- Route of administration
- ORAL
- Max daily dose
- 60 mg milligram(s)
- Max total dose
- 60 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09AA15 — ZOFENOPRIL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP109534428 · ATC
- Active substance
- Bisoprolol Fumarate
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C07AB07 — BISOPROLOL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP126600 · ATC
- Active substance
- Perindopril Tert-Butylamine
- Substance synonyms
- PERINDOPRIL ERBUMINE
- Route of administration
- ORAL
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 100 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C07AG02 — CARVEDILOL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1000156 · ATC
- Active substance
- Valsartan
- Route of administration
- ORAL
- Max daily dose
- 320 mg milligram(s)
- Max total dose
- 320 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09CA03 — VALSARTAN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP162949 · ATC
- Active substance
- Eprosartan Mesilate
- Substance synonyms
- EPROSARTAN MESYLATE, 4-[[2-BUTYL-5-[(E)-2-CARBOXY-3-THIOPHEN-2-YL-PROP-1-ENYL]IMIDAZOL-1-YL]METHYL]BENZOIC ACID: METHANESULFONIC ACID
- Route of administration
- ORAL
- Max daily dose
- 800 mg milligram(s)
- Max total dose
- 800 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09CA02 — EPROSARTAN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP10361725 · ATC
- Active substance
- Hydrochlorothiazide
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09AA05 — RAMIPRIL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP131775 · ATC
- Active substance
- Valsartan
- Route of administration
- ORAL
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 300 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09CA04 — IRBESARTAN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1150567 · ATC
- Active substance
- Nebivolol
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C07AB12 — NEBIVOLOL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP129505 · ATC
- Active substance
- Enalapril Maleate
- Substance synonyms
- Enalapril hydrogen maleate
- Route of administration
- ORAL
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 40 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09AA02 — ENALAPRIL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP128457 · ATC
- Active substance
- Candesartan
- Route of administration
- ORAL
- Max daily dose
- 32 mg milligram(s)
- Max total dose
- 32 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09CA06 — CANDESARTAN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1166632 · ATC
- Active substance
- Quinapril Hydrochloride
- Route of administration
- ORAL
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 40 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09AA06 — QUINAPRIL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Medical University Of Vienna
- Sponsor organisation
- Medical University Of Vienna
- Address
- Spitalgasse 23, Alsergrund Alsergrund
- City
- Vienna
- Postcode
- 1090
- Country
- Austria
Scientific contact point
- Organisation
- Medical University Of Vienna
- Contact name
- Department of Cardiology
Public contact point
- Organisation
- Medical University Of Vienna
- Contact name
- Department of Cardiology
Locations
2 EU/EEA countries · 11 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Austria | Authorised, recruitment pending | 405 | 9 |
| Spain | Authorised, recruitment pending | 43 | 2 |
| Rest of world
United Kingdom, New Zealand
|
— | 441 | — |
Investigational sites
Medical University Of Vienna
Klin. Abtlg. für Endokrinologie und Stoffwechsel, Waehringer Guertel 18-20, Alsergrund, Vienna
Medical University Of Vienna
Department of Cardiology, Waehringer Guertel 18-20, Alsergrund, Vienna
Imed19-Privat
Imed19 Privat, Chimanistrasse 1, Doebling, Vienna
Medical University Of Vienna
Universitätsklinik für Augenheilkunde und Optometrie, Waehringer Guertel 18-20, Alsergrund, Vienna
ÖGK Mein Gesundheitszentrum Favoriten
Diabetesambulanz, Wienerbergstraße 13, 1100, Wien
Medical University Of Graz
Klin. Abtlg. für Endokrinologie und Diabetologie, Neue Stiftingtalstrasse 6, 8010, Graz
Ordination Dr. Feinböck
Internistische Ordination Dr. Feinböck, Fleischgasse 1/2, 2340, Mödling
Konvent Der Barmherzigen Brueder
Abtlg. für Innere Medizin, Seilerstaette 2, 4020, Linz
Dr. Distelmaier & Dr. Goliasch Gruppenpraxis Fuer Innere Medizin Und Kardiologie OG
Herzzentrum Währing, Theresiengasse 43/7, 1180, Vienna
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 47 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2024-516923-15-00_v5-4_23MAY2023_redacted | 5.4 |
| Protocol (for publication) | D1_Protocol_Substudy-echo_v1-0_19Apr2016 | 1 |
| Protocol (for publication) | D1_Protocol_Substudy-eye_v1-4_24Aug2020_redacted | 1.4 |
| Recruitment arrangements (for publication) | K1_Recruitment-Arrangements_18Oct2024 | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment-Arrangements_18Oct2024 | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Master_AUT_v6-3_3Nov2022 | 6.3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Master-ES_v4-0_19Sep23 | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Substudy-eye_Diabetiker_v1-9_11Feb2021 | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Substudy-eye_Gesunde_v1-1_12Dec2019 | 1 |
| Subject information and informed consent form (for publication) | L1_Site-contact-list_AT_v3-3_24May2023 | 3.3 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Accupro_1Aug2015 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Acemin_01May2015 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Bisoprolol_1Oct2022 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Blopress_01Aug2014 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Candesartan_1Aug2021 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Captopril_1Jun2021 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Captopril_1Oct2014 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Carvedilol_1Sep2024 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Cilazapril_1Apr2022 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Concor_1Sep2015 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Cosaar_1Nov2013 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Coversum_1Feb2015 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Dilatrend_1Jan2014 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Diovan_1Apr2015 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Enalapril_1Jul2021 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Eprosartan_1Jun2022 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Fosinopril_1Nov2019 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Fositens_1Feb2015 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Inhibace_1Sep2014 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Irbepress_1Jun2015 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Irbesartan_1Jul2021 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Lisinopril_1Jul2021 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Losartan_1Nov2020 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Metoprolol_1Aug2021 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Nebivolol_1Sep2022 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Nomexor_1Jan2015 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Perindopril_1Jan2019 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Quadropril_1Mar2010 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Quinapril_1Feb2023 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Ramipril_1Oct2019 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Renitec_1Aug2015 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Seloken-retard_1Aug2014 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Teveten_1Jan2015 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Tritace_1Aug2015 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Valsartan_1Dec2020 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Zofenil_1Nov2014 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_v5-2_01Feb2016_redacted | 5.2 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-12-19 | Austria | Acceptable 2025-02-14
|
2025-02-14 |