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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02817360




Registration number
NCT02817360
Ethics application status
Date submitted
15/02/2016
Date registered
29/06/2016
Date last updated
14/03/2023

Titles & IDs
Public title
NT-proBNP Selected Prevention of Cardiac Events in Diabetic Patients
Scientific title
NT-proBNP Selected PreventiOn of Cardiac eveNts in a populaTion of dIabetic Patients Without A History of Cardiac Disease: a Prospective Randomized Trial
Secondary ID [1] 0 0
PONTIAC II
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Diseases 0 0
Diabetes Mellitus, Type 2 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - RAS-antagonist and beta-blocker up-to maximal dosages
Other interventions - RAS-antagonist and beta-blocker none or at stable dose

Experimental: Intensive therapy - RAS-antagonist and beta-blocker up-to maximal dosages as permitted and tolerated and following national guidelines.

Other: Conventional therapy - No RAS-antagonist and beta-blocker or at stable dose as per study entrance. Changes in RAS-antagonist or beta-blocker therapy are not allowed in the control group during the study phase.


Treatment: Drugs: RAS-antagonist and beta-blocker up-to maximal dosages
All patients have to be stable on their glucose lowering, lipid lowering and blood pressure lowering therapy at least for 3 months. RAS-antagonist and beta-blocker therapy at entrance is allowed. Patients receive a prescription and/or up-titration to maximum recommended or tolerated dose of RAS-antagonist and beta-blockers within three months of study entry. The Number of titration visits is up to the treating physician, but one visit should be performed at least at the end of titration.

Other interventions: RAS-antagonist and beta-blocker none or at stable dose
All patients have to be stable on their glucose lowering, lipid lowering and blood pressure lowering therapy at least for 3 months. RAS-antagonist and beta-blocker therapy at entrance is allowed. Changes in RAS-antagonist or beta-blocker therapy are not allowed in the control group during the study phase. If there is a vital indication for changes, this has to be argued and documented.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of patients with an unplanned cardiac hospitalization or death due to a cardiac event
Timepoint [1] 0 0
2 years

Eligibility
Key inclusion criteria
1. Type-2 diabetes for at least six months,
2. = 18 years of age, men or female,
3. Written informed consent to participate in the study and ability to comply with all requirements.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of hypersensitivity to any of the investigated drugs as well as known or suspected contraindications to the study drugs or previous history of intolerance to high dose of RAS-Antagonist or Beta-blocker in the absence of any other blood pressure lowering drugs.
2. Patients already on maximum dose of RAS-antagonist or beta-blocker.
3. Creatinine > 2.5mg/dl.
4. Symptomatic hypotension and/or systolic blood pressure (SBP) < 100 mmHg at Visit 1.
5. Symptomatic bradycardia and/or heart rate (HR) < 60 bpm at Visit 1
6. Signs of cardiac disease in the ECG such as atrial fibrillation; ST-T abnormalities or any bundle branch block / higher degree atrioventricular (AV) block.
7. Abnormal echocardiography, defined as low ejection fraction < 50%; wall motion abnormalities suggesting coronary artery disease (CAD), significant valve dysfunction > grade I or other significant alteration.
8. 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.
9. A disease other than T2DM lowering the patient's life expectancy to less than two years.
10. Chronic infections or malignancies.
11. Systemic treatment with corticosteroids.
12. Renal replacement therapy.
13. 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 > 40 mIU/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.
14. 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 (> 5 U/ml).
15. History of noncompliance to medical regimes and patients who are considered potentially unreliable.
16. Current double blind treatment in diabetic trials.
17. Participation in an investigational drug study at the time of enrollment or within the past 90 days.

Eligibility criteria for eye-substudy:

Inclusion criteria:

1. Participation in the PONTIAC 2 Study
2. Written informed consent to participate in the eye-study

Exclusion criteria:

1. Media opacities like cataract or vitreous hemorrhage
2. Active intraocular inflammation (grade trace or above) in either eye like infectious conjunctivitis, keratitis, scleritis, endophthalmitis as well as idiopathic or autoimmune-associated uveitis in either eye
3. Structural damage to the center of macula in the study eye
4. Atrophy of retinal pigment epithelium, subretinal fibrosis, laser scar within foveal avascular zone (FAZ) or organized hard exudate plaques
5. Ocular disorders in the study eye including retinal vascular occlusion, retinal detachment, macular hole, choroidal neovascularization, macula dystrophies
6. Intraocular surgery (including cataract surgery, Yttrium-Aluminium-Granat (YAG) laser capsulotomy) in the study eye within 3 months preceding Day 0
7. Uncontrolled glaucoma in the study eye (defined as intraocular pressure = 25 mmHg despite treatment with anti-glaucoma medication)
8. History of glaucoma filtration surgery, corneal transplantation in the study eye
9. Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality to be analyzed and graded
10. History of epilepsy

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2026
Actual
Sample size
Target
2400
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Niederösterreich
Country [2] 0 0
Austria
State/province [2] 0 0
Steiermark
Country [3] 0 0
Austria
State/province [3] 0 0
Upper Austria
Country [4] 0 0
Austria
State/province [4] 0 0
Vienna
Country [5] 0 0
Austria
State/province [5] 0 0
Wien
Country [6] 0 0
Netherlands
State/province [6] 0 0
Maastricht
Country [7] 0 0
New Zealand
State/province [7] 0 0
Christchurch
Country [8] 0 0
Spain
State/province [8] 0 0
Barcelona
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Dundee
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Glasgow
Country [11] 0 0
United Kingdom
State/province [11] 0 0
Manchester
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Other
Name
Martin Huelsmann
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Purpose and rationale The purpose of this study is to evaluate the effect of high dose Renin-Angiotensin System (RAS)-antagonists and beta-blocker treatment for the primary prevention of cardiac events in a population of patients with Type 2 diabetes mellitus (T2DM) with no evidence of a preexisting cardiac disease. An additional aim is to demonstrate an interaction between concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP as a surrogate of imminent cardiac risk) and treatment effects and the economic impact of the intervention overall and in the biomarker stratified subgroups.

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 with a NT-proBNP \> 125pg/ml.

There is an additional eye-substudy for Viennese sites only. The purpose of this sub-study is to evaluate the effect of high dose RAS-antagonists and beta blocker treatment on early subclinical signs of diabetic micro-angiopathy and neuropathy. An additional aim will be the evaluation of the possible impact of the cardiovascular risk factor NT-proBNP on the onset and progression of diabetic retinopathy.
Trial website
https://clinicaltrials.gov/study/NCT02817360
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Martin Huelsmann, Doz.Dr.
Address 0 0
Univ.Clinic II, Medical University Vienna
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Martin Huelsmann, Doz.Dr.
Address 0 0
Country 0 0
Phone 0 0
+43 1 40400
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02817360