Clinical trial • Phase IV • Cardiology|Endocrinology

EPROSARTAN MESILATE for Type 2 diabetes

Phase IV trial of EPROSARTAN MESILATE for Type 2 diabetes.

Overview

Trial Therapeutic Area
Cardiology|Endocrinology
Trial Disease
Type 2 diabetes
Trial Stage
Phase IV
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
19-12-2024
First CTIS Authorization Date
14-02-2025

Trial design

Randomised, high-dose treatment with ras-antagonists and beta-blockers versus conventional therapy (trial compares intensified/high-dose ras-antagonists + beta-blockers against standard/conventional therapy). specific agents listed as possible ras-antagonists/ace-inhibitors/arbs and beta-blockers in the protocol include eprosartan (max 800 mg), enalapril (max 40 mg), cilazapril (max 5 mg), lisinopril (max 40 mg), perindopril (max 8 mg), ramipril (max 10 mg), fosinopril (max 40 mg), quinapril (max 40 mg), captopril (max 150 mg), various arbs (losartan up to 150 mg, valsartan up to 320 mg, candesartan up to 32 mg, irbesartan up to 300 mg, eprosartan), and beta-blockers (metoprolol up to 200 mg, bisoprolol up to 10 mg, nebivolol up to 10 mg, carvedilol up to 100 mg). (dose information is the listed maximum daily dose per product record; schedule not otherwise specified.)-controlled Phase IV trial in Austria, Spain.

Randomised
Yes
Comparator
High-dose treatment with RAS-antagonists and beta-blockers versus conventional therapy (trial compares intensified/high-dose RAS-antagonists + beta-blockers against standard/conventional therapy). Specific agents listed as possible RAS-antagonists/ACE-inhibitors/ARBs and beta-blockers in the protocol include eprosartan (max 800 mg), enalapril (max 40 mg), cilazapril (max 5 mg), lisinopril (max 40 mg), perindopril (max 8 mg), ramipril (max 10 mg), fosinopril (max 40 mg), quinapril (max 40 mg), captopril (max 150 mg), various ARBs (losartan up to 150 mg, valsartan up to 320 mg, candesartan up to 32 mg, irbesartan up to 300 mg, eprosartan), and beta-blockers (metoprolol up to 200 mg, bisoprolol up to 10 mg, nebivolol up to 10 mg, carvedilol up to 100 mg). (Dose information is the listed maximum daily dose per product record; schedule not otherwise specified.)
Biomarker Stratified
True, biomarker: NT-proBNP; strata described include NT-proBNP > 125 pg/ml (co-primary analysis) and the whole population
Target Sample Size
448

Eligibility

Recruits 448 No vulnerable population selected. Written informed consent from each participant is required (see inclusion criterion: "Written informed consent to participate in the study and ability to comply with all requirements"). Subject information and informed consent form documents are provided (Master ICF available for Austria and Spain)..

Pregnancy Exclusion
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).
Vulnerable Population
No vulnerable population selected. Written informed consent from each participant is required (see inclusion criterion: "Written informed consent to participate in the study and ability to comply with all requirements"). Subject information and informed consent form documents are provided (Master ICF available for Austria and Spain).

Inclusion criteria

  • {"criterion_text":"- Type-2 diabetes mellitus for at least six months"}
  • {"criterion_text":"- ≥18 years of age,men or female"}
  • {"criterion_text":"- Written informed consent to participate in the study and ability to comply with all requirements"}

Exclusion criteria

  • {"criterion_text":"- 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"}
  • {"criterion_text":"- Patients already receiving a maximum dose of RAAS-antagonists or beta-blocker"}
  • {"criterion_text":"- Creatinine>2.5mg/dl"}
  • {"criterion_text":"- Symptomatic hypotension and/or systolic blood pressure(SBP) <100mmHg at visit 1"}
  • {"criterion_text":"- Symptomatic bradycardia and/or heart rate (HR)<60bpm at visit 1"}
  • {"criterion_text":"- Signs of cardiac disease in the electrocardiogram, such as atrial fibrillation, ST-T 
abnormalities, or a bundle branch block/ higher degree AV block"}
  • {"criterion_text":"- Abnormal echocardiography, defined as low ejection fraction <50%; wall motion abnormalities suggesting coronary artery disease (CAD), significant valve dysfunction > grades I."}
  • {"criterion_text":"- 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"}
  • {"criterion_text":"- A disease other than diabetes lowering the patient’s life expectancy to less than two years."}
  • {"criterion_text":"- Exclusion criteria specific for Spain only"}
  • {"criterion_text":"- Chronic infections or malignancies"}
  • {"criterion_text":"- Systemic treatment with corticosteroids"}
  • {"criterion_text":"- Renal replacement therapy"}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- 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)."}
  • {"criterion_text":"- History of noncompliance to medical regimes and patients who are considered potentially unreliable"}
  • {"criterion_text":"- Current double blind treatment in diabetic trials"}
  • {"criterion_text":"- Participation in an investigational drug study at the time of enrollment or within the past 90 days."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Combined endpoint based on the first occurrence of cardiac death and cardiac hospitalization.","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- All cardiac hospitalization","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Heart failure hospitalization","definition_or_measurement_approach":""}
  • {"endpoint_text":"- All cause hospitalization","definition_or_measurement_approach":""}
  • {"endpoint_text":"- NT-proBNP","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Other predefined (see section plasma and serum biomarkers) biomarkers","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Health economic analysis (cost-effectiveness of intervention considering both life- years and quality of life adjusted life years)","definition_or_measurement_approach":""}

Recruitment

Planned Sample Size
448
Recruitment Window Months
119
Consent Approach
Written informed consent is required from each participant (adult participants ≥18 provide consent). Subject information and ICF documents are provided (Master ICF for Austria: L1_SIS and ICF_Master_AUT_v6-3; Master ICF for Spain: L1_SIS and ICF_Master-ES_v4-0). ICFs presumptively available in local languages (German for Austria and Spanish for Spain).

Geography

Total Number Of Sites
11
Total Number Of Participants
448

Austria

Earliest CTIS Part Ii Submission Date
21-01-2025
Latest Decision Or Authorization Date
17-02-2025
Processing Time Days
27
Number Of Sites
9
Number Of Participants
405

Sites

Site Name
Imed19-Privat
Department Name
Imed19 Privat
Principal Investigator Name
Christopher Adlbrecht
Principal Investigator Email
c.adlbrecht@imed19.at
Contact Person Name
Christopher Adlbrecht
Contact Person Email
c.adlbrecht@imed19.at
Site Name
Medical University Of Vienna
Department Name
Department of Cardiology
Principal Investigator Name
Martin Hülsmann
Principal Investigator Email
Martin.huelsmann@meduniwien.ac.at
Contact Person Name
Martin Hülsmann
Site Name
Medical University Of Graz
Department Name
Klin. Abtlg. für Endokrinologie und Diabetologie
Principal Investigator Name
Harald Sourij
Principal Investigator Email
ha.sourij@medunigraz.at
Contact Person Name
Harald Sourij
Contact Person Email
ha.sourij@medunigraz.at
Site Name
Medical University Of Vienna
Department Name
Universitätsklinik für Augenheilkunde und Optometrie
Principal Investigator Name
Julia Aschauer
Principal Investigator Email
julia.aschauer@meduniwien.ac.at
Contact Person Name
Julia Aschauer
Site Name
Konvent Der Barmherzigen Brueder
Department Name
Abtlg. für Innere Medizin
Principal Investigator Name
Martin Clodi
Principal Investigator Email
martin.clodi@bblinz.at
Contact Person Name
Martin Clodi
Contact Person Email
martin.clodi@bblinz.at
Site Name
Ordination Dr. Feinböck
Department Name
Internistische Ordination Dr. Feinböck
Principal Investigator Name
Christian Feinböck
Principal Investigator Email
office@dr-feinboeck.at
Contact Person Name
Christian Feinböck
Contact Person Email
office@dr-feinboeck.at
Site Name
ÖGK Mein Gesundheits­zentrum Favoriten
Department Name
Diabetesambulanz
Principal Investigator Name
Helmut Brath
Principal Investigator Email
helmut.brath@oegk.at
Contact Person Name
Helmut Brath
Contact Person Email
helmut.brath@oegk.at
Site Name
Medical University Of Vienna
Department Name
Klin. Abtlg. für Endokrinologie und Stoffwechsel
Principal Investigator Name
Alexandra Kautzky-Willer
Principal Investigator Email
alexandra.kautzky-willer@meduniwien.ac.at
Contact Person Name
Alexandra Kautzky-Willer
Site Name
Dr. Distelmaier & Dr. Goliasch Gruppenpraxis Fuer Innere Medizin Und Kardiologie OG
Department Name
Herzzentrum Währing
Principal Investigator Name
Georg Goliasch
Principal Investigator Email
ordination@herzzentrum18.at
Contact Person Name
Georg Goliasch
Contact Person Email
ordination@herzzentrum18.at

Spain

Earliest CTIS Part Ii Submission Date
21-01-2025
Latest Decision Or Authorization Date
14-02-2025
Processing Time Days
24
Number Of Sites
2
Number Of Participants
43

Sites

Site Name
Hospital Germans Trias I Pujol
Department Name
l'Institut del Cor
Principal Investigator Name
Antoni Bayes-Genis
Principal Investigator Email
abayesgenis@gmail.com
Contact Person Name
Antoni Bayes-Genis
Contact Person Email
abayesgenis@gmail.com
Site Name
Hospital De La Santa Creu I Sant Pau
Department Name
Unitat de Diabetis, Servei d'Endocrinologia i Nutrició
Principal Investigator Name
Rosa Corcoy
Principal Investigator Email
rcorcoy@santpau.cat
Contact Person Name
Rosa Corcoy
Contact Person Email
rcorcoy@santpau.cat

Sponsor

Primary sponsor

Full Name
Medical University Of Vienna
Organisation Type
Educational Institution
Country Of Registered Address
Austria

Investigational products

Investigational Product Name
EPROSARTAN
Active Substance
EPROSARTAN MESILATE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
800 mg
Investigational Product Name
ZOFENOPRIL
Active Substance
ZOFENOPRIL CALCIUM
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
60 mg
Investigational Product Name
QUINAPRIL
Active Substance
QUINAPRIL HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
40 mg
Investigational Product Name
RAMIPRIL
Active Substance
HYDROCHLOROTHIAZIDE, RAMIPRIL
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
10 mg
Investigational Product Name
FOSINOPRIL
Active Substance
FOSINOPRIL SODIUM
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
40 mg
Investigational Product Name
CARVEDILOL
Active Substance
PERINDOPRIL TERT-BUTYLAMINE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
100 mg
Investigational Product Name
NEBIVOLOL
Active Substance
NEBIVOLOL
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
10 mg
Investigational Product Name
LOSARTAN
Active Substance
LOSARTAN POTASSIUM, HYDROCHLOROTHIAZIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
150 mg
Investigational Product Name
PERINDOPRIL
Active Substance
PERINDOPRIL TERT-BUTYLAMINE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
8 mg
Investigational Product Name
SPIRAPRIL
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
24 mg
Investigational Product Name
CILAZAPRIL
Active Substance
CILAZAPRIL
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
5 mg
Investigational Product Name
BISOPROLOL
Active Substance
BISOPROLOL FUMARATE, HYDROCHLOROTHIAZIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
10 mg
Investigational Product Name
CANDESARTAN
Active Substance
CANDESARTAN
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
32 mg
Investigational Product Name
METOPROLOL
Active Substance
METOPROLOL SUCCINATE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
200 mg
Investigational Product Name
IRBESARTAN
Active Substance
VALSARTAN
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
300 mg
Investigational Product Name
ENALAPRIL
Active Substance
ENALAPRIL MALEATE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
40 mg
Investigational Product Name
LISINOPRIL
Active Substance
LISINOPRIL DIHYDRATE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
40 mg
Investigational Product Name
VALSARTAN
Active Substance
VALSARTAN, HYDROCHLOROTHIAZIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
320 mg
Investigational Product Name
Captopril
Active Substance
CAPTOPRIL, HYDROCHLOROTHIAZIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
150 mg
Combination Treatment
Yes

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