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NT-proBNP Selected Prevention of Cardiac Events in Diabetic Patients

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ClinicalTrials.gov Identifier: NCT02817360
Recruitment Status : Recruiting
First Posted : June 29, 2016
Last Update Posted : March 14, 2023
Sponsor:
Information provided by (Responsible Party):
Martin Huelsmann, Medical University of Vienna

Study Description
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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.


Condition or disease Intervention/treatment Phase
Heart Diseases Diabetes Mellitus, Type 2 Drug: RAS-antagonist and beta-blocker up-to maximal dosages Other: RAS-antagonist and beta-blocker none or at stable dose Phase 4

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Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: NT-proBNP Selected PreventiOn of Cardiac eveNts in a populaTion of dIabetic Patients Without A History of Cardiac Disease: a Prospective Randomized Trial
Study Start Date : February 2016
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Diseases

Arms and Interventions
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Arm Intervention/treatment
Experimental: Intensive therapy
RAS-antagonist and beta-blocker up-to maximal dosages as permitted and tolerated and following national guidelines.
 Drug: 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 Names:
  • Enalapril 40mg/d
  • Ramipril 10mg/d
  • Lisinopril 40mg/d
  • Cilazapril 5mg/d
  • Perindopril 8mg/d
  • Captopril 150mg/d
  • Spirapril 24mg/d
  • Quinapril 40mg/d
  • Trandolapril 4mg/d
  • Zofenopril 60mg/d
  • Fosinopril 40mg/d
  • Candesartan 32mg/d
  • Valsartan 320mg/d
  • Irbesartan 300mg/d
  • Losartan 150mg/d
  • Eprosartan 800mg/d
  • Bisoprolol 10mg/d
  • Metoprololsuccinat 200mg/d
  • Carvedilol 50mg/d (100mg/d if weight is > 85kg)
  • Nebivolol 10mg/d
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.
 Other: 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.


Outcome Measures
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Primary Outcome Measures :
  1. Number of patients with an unplanned cardiac hospitalization or death due to a cardiac event [ Time Frame: 2 years ]
    The combined endpoint of the number of patients with an unplanned cardiac hospitalization or death due to a cardiac event will be recorded throughout the study duration of 2 years.


Other Outcome Measures:
  1. Number of patients hospitalised due to any cardiac reasons [ Time Frame: 2 years ]
    The number of subjects who were hospitalised due to any cardiac reasons will recorded.

  2. Number of patients hospitalised due to heart failure [ Time Frame: 2 years ]
    The number of subjects who were hospitalised due to a heart failure will recorded.

  3. Number of patients hospitalised due to all causes [ Time Frame: 2 years ]
    The number of subjects who were hospitalised due to any cause

  4. Change of kidney function [ Time Frame: 2 years ]
    Change of kidney function measured by eGFR (estimated glomerular filtration rate)


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02817360


Contacts
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Contact: Martin Huelsmann, Doz.Dr. +43 1 40400 ext 46140 martin.huelsmann@meduniwien.ac.at

Locations
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Sponsors and Collaborators
Martin Huelsmann
Investigators
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Principal Investigator: Martin Huelsmann, Doz.Dr. Univ.Clinic II, Medical University Vienna
More Information
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Responsible Party: Martin Huelsmann, Univ.Doz. Dr., Medical University of Vienna
ClinicalTrials.gov Identifier: NCT02817360    
Other Study ID Numbers: PONTIAC II
First Posted: June 29, 2016    Key Record Dates
Last Update Posted: March 14, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Heart Diseases
Diabetes Mellitus, Type 2
Cardiovascular Diseases
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Losartan
Valsartan
Carvedilol
Candesartan
Ramipril
Enalapril
Lisinopril
Irbesartan
 Nebivolol
Bisoprolol
Perindopril
Captopril
Quinapril
Trandolapril
Fosinopril
Eprosartan
Zofenopril
Spirapril
Cilazapril
Adrenergic beta-Antagonists
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists