Heart DiseasesPhase 4NCT02817360
NT-proBNP Selected Prevention of Cardiac Events in Diabetic Patients
A Phase 4 study testing RAS-antagonist and beta-blocker up-to maximal dosages and RAS-antagonist and beta-blocker none or at stable dose in people with Heart Diseases and Diabetes Mellitus, Type 2, run by Martin Huelsmann at 21 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Diseases, Diabetes Mellitus, Type 2
- What is being tested?
- RAS-antagonist and beta-blocker up-to maximal dosages and RAS-antagonist and beta-blocker none or at stable dose
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,400 participants
- Where
- 21 sitesin 5 countries
- Study dates
- Feb 2016to Dec 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type-2 diabetes 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.
- Participation in the PONTIAC 2 Study
- Written informed consent to participate in the eye-study
Who cannot join
- 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.
- Patients already on maximum dose of RAS-antagonist or beta-blocker.
- Creatinine > 2.5mg/dl.
- Symptomatic hypotension and/or systolic blood pressure (SBP) < 100 mmHg at Visit 1.
- Symptomatic bradycardia and/or heart rate (HR) < 60 bpm at Visit 1
- Signs of cardiac disease in the ECG such as atrial fibrillation; ST-T abnormalities or any bundle branch block / higher degree atrioventricular (AV) block.
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- 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.
- 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 T2DM lowering the patient's life expectancy to less than two years.
- 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 > 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.
- 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).
- 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.
- Eligibility criteria for eye-substudy:
- Media opacities like cataract or vitreous hemorrhage
- 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
- Structural damage to the center of macula in the study eye
- Atrophy of retinal pigment epithelium, subretinal fibrosis, laser scar within foveal avascular zone (FAZ) or organized hard exudate plaques
- Ocular disorders in the study eye including retinal vascular occlusion, retinal detachment, macular hole, choroidal neovascularization, macula dystrophies
- Intraocular surgery (including cataract surgery, Yttrium-Aluminium-Granat (YAG) laser capsulotomy) in the study eye within 3 months preceding Day 0
- Uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥ 25 mmHg despite treatment with anti-glaucoma medication)
- History of glaucoma filtration surgery, corneal transplantation in the study eye
- Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality to be analyzed and graded
- History of epilepsy
Trial locations and contacts
21 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
21 sites in 5 countries
Austria11 sites, 7 recruiting
- Recruiting
Klinischen Abteilung für Endokrinologie und Diabetologie MU Graz
Graz, Styria, 8036
Harald Sourij, +43-316-385-80363, ha.sourij@medunigraz.at
Michael Zink, +43-680-128-5120, m.zink@medunigraz.at
- Recruiting
Konventhospital der Barmherzigen Brüder Abteilung für Innere Medizin
Linz, Upper Austria, 4021
Martin Clodi, Prof.Dr., martin.clodi@bblinz.at
Martin Clodi, Prof.Dr.
- Active, not recruiting
Internistische Ordination
Mödling, Lower Austria, 2340
- Completed
Krankenanstalt Rudolfstiftung, 1. Medizinische Abteilung
Vienna, 1030
- Terminated
Zentrum für Klinische Studien
Vienna, 1060
- Recruiting
Medical University of Vienna Univ.Clinic for Internal Medicine II Department of Cardiology
Vienna, 1090
Martin Huelsmann, Doz.Dr., +43 1 40400 ext. 46140, martin.huelsmann@meduniwien.ac.at
Martin Huelsmann, Doz.Dr.
- Recruiting
Univ. Klinik für Innere Medizin III Med. Uni Wien
Vienna, 1090
Alexandra Kautzky-Willer, Prof.Dr., 00 43 1 40400 ext. 43100, alexandra.kautzky-willer@meduniwien.ac.at
Alexandra Kautzky-Willer, Prof.Dr.
- Recruiting
Universitätsklinik für Augenheilkunde und Optometrie Medizinische Universität Wien
Vienna, 1090
Sonja Karst, Dr., +43 1 40400 ext. 79470, sonja.karst@meduniwien.ac.at
Sonja Karst (prev. Prager), Dr.
- Recruiting
Diabetes & Stoffwechselambulanz Gesundheitszentrum Wien Süd
Vienna, 1100
Helmut Brath, OA Dr., +43 1 60122 ext. 4264, helmut.brath@wgkk.at
Helmut Brath, OA Dr.
- Terminated
3. Med. Abtlg., KH Hietzing mit Neurologischem Zentrum Rosenhügel
Vienna, 1130
- Recruiting
iMED19
Vienna, 1190
Christopher Adlbrecht, PD Dr., c.adlbrecht@imed19.at
United Kingdom6 sites, 3 recruiting
- Recruiting
Ninewells Hospital, Diabetes Support Unit
Dundee, DD19SY
Rory McCrimmon, MD Prof, r.mccrimmon@dundee.ac.uk
- Recruiting
Queen Elisabeth University Hospital, Glasgow Clinical Research Facility
Glasgow, G514TF
Pierpaolo Pellicori, MD Prof, pierpaolo.pellicori@glasgow.ac.uk
- Recruiting
North Manchester General Hospital, Diabetes centre
Manchester, M85RB
Cuong Dang, MD Prof, Cuong.dang@mft.nhs.uk
- Active, not recruiting
Nethergreen Surgery
Sheffield, S117EJ
- Active, not recruiting
Ecclesfield Group Practice
Sheffield, S359XQ
- Active, not recruiting
Woodseats Medical Centre
Sheffield, S8OSH
Spain2 sites, 2 recruiting
- Recruiting
Hospital de la Santa Creu i Sant Pau, Unitat de Diabetis, Servei d'Endocrinologia i Nutrició, Universitat Autònoma de Barcelona
Barcelona, 8025
Rosa Corcoy, MD Prof, RCorcoy@santpau.cat
- Recruiting
Hospital Universitari Germans Trias i Pujol, l'Institut del Cor
Barcelona, 8916
Antoni Bayes-Genis, MD Prof, abayesgenis@gmail.com
Netherlands1 site
- Active, not recruiting
Maastricht University Medical Center; Dep. Cardiology
Maastricht, 6202
New Zealand1 site, 1 recruiting
- Recruiting
Christchurch Heart Institute
Christchurch, 8140
Richard Troughton, MD Prof, +64 3 364 1063, Richard.Troughton@cdhb.health.nz
Lorraine Skelton, +64 3 364 1063, lorraine.skelton@cdhb@health.nz
About this study
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
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.
Read the detailed description
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.
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 objective 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).
Population The study population will consist of patients with T2DM without any history or signs of cardiac disease. Patients from approximately 20 centers worldwide will be included into the study and randomized 1:1 to intensive or conventional therapy. It is estimated that about 3000 patients have to be screened In order to include 2400 patients. The screen failure rate is anticipated to be approximately 20%.
Investigational and reference therapy All eligible patients will be randomized to receive either a high dose of RAS-antagonists and beta-blockers (as defined in the section investigational drugs) on top of standard diabetes therapy or solely standard diabetes therapy. The use of RAS-antagonist and beta-blocker therapy at randomization is allowed in the control group (with the exception of maximal dosage), but prescription or titration during the study period is not encouraged. However, if the investigators feel that further prescription or up-titration is required a thorough justification is mandatory. Every attempt should be made to use other blood pressure lowering drugs than RAS-antagonists or beta-blockers in the control group.
Study design This study is a randomized open-label, parallel group, active-controlled, two-arm, long-term morbidity and mortality trial to evaluate the efficacy and safety of high dose RAS-antagonist and beta-blocker therapy (as defined in the section investigational drugs) compared to standard diabetes therapy in patients with diabetes without any history or sign of a cardiac disease.
The goal is to include 2400 patients. The observation period is planned to last for two years. However, the trial is event driven and will continue until predefined event rate is reached. The total trial duration is expected to last for four years (two years of recruitment and a two year observation period after last patient in). Every patient will remain in the study for two years after randomization.
Visit 1 Screening At the first visit eligibility to enter the study will be assessed by the investigator. All inclusion/exclusion criteria will be evaluated. Informed consent will be obtained. Demographic data and drug prescription will be assessed. Blood will be obtained. Blood chemistry will be assessed locally. NT-proBNP will be determined by a point of care system locally. The investigator will be blinded to the result, which will be sent to the central computer. Blood will be obtained for the core lab, centrifuged and stored at -80° Celsius at the local unit. Vital signs will be obtained. Randomization will be performed electronically, this way randomization can be performed immediately.
Visit 2 (3 months) At visit 2 vital signs will be obtained. Blood will be drawn. Blood chemistry parameters will be assessed locally for safety reason. Drug prescription will be documented.
Visit 3 (12 months) At visit 3 vital signs will be obtained. Blood will be drawn. Blood chemistry parameters will be assessed locally for safety reason. Drug prescription will be documented.
Visit 4 EOS (end of study) (24 months) At visit 4 vital signs will be obtained. Blood will be drawn. Blood chemistry parameters will be assessed locally for safety reason. Additional blood samples will be sent to the core laboratory. Drug prescription will be documented.
Visit 1-4 is mandatory for all patients. Long-term follow-up Patients with be further followed by population register or telephone contact respectively until completion of the study to determine long-term mortality and hospitalizations.
Unscheduled visits for the treatment group The treatment group will have additional visits for up-titration of RAS-antagonists and beta- blocker between visit 1 and visit 2. The frequency is up to the treating physician and dependent on the titration steps. A visit is not mandatory for each titration step. Patients will receive a logbook by the investigator, with weekly up- titration steps of the drugs. Additionally, patients will receive a diary for daily documentation of blood pressure, heart rate and symptoms if measurement is technically feasible for the patient. Based on own measurements, these data and laboratory results the investigator will decide if further up-titration of medication is possible. Systolic blood pressure should not decrease permanently below 100 mmHg and heart not below 60bpm permanently. Recommended drugs and recommended dosages are outlined in the section "Treatment". At each visit, blood chemistry for eGFR, creatinine, blood urea nitrogen (BUN), sodium and potassium will be obtained for safety reason.
Details of the eye-substudy:
The PONTIAC Eye Study is a masked longitudinal follow up of previously 1:1 randomized study patients participating in the PONTIAC 2 study. It is planed to include 130 consecutive patients for biannually visits over a study period of 2 years. Study patients (n=130) will be assigned to the Department of Ophthalmology and Optometry of the Medical University Vienna once they are included in the PONTIAC 2 Study in one of the participating Centers in Vienna. The investigators will be masked to the patient's randomization.
The primary objective of the sub-study is: Superiority of the treatment arm with RAS-antagonists and beta-blockers compared to conventional therapy regarding thickness-change in the retinal nerve fiber layer or outer nuclear layer measured in spectral domain optical coherence tomography.
- Conditions
- Heart Diseases, Diabetes Mellitus, Type 2
- Being tested
- RAS-antagonist and beta-blocker up-to maximal dosages, RAS-antagonist and beta-blocker none or at stable dose
- Medical subject headings
- Heart Diseases, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAS-antagonist and beta-blocker up-to maximal dosagesDrug
Also called Enalapril 40mg/d, Ramipril 10mg/d, Lisinopril 40mg/d, Cilazapril 5mg/d
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.
RAS-antagonist and beta-blocker none or at stable doseOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Intensive therapy | Experimental | RAS-antagonist and beta-blocker up-to maximal dosages as permitted and tolerated and following national guidelines. Receives: Drug: RAS-antagonist and beta-blocker up-to maximal dosages |
| Conventional therapy | Other | 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. Receives: Other: RAS-antagonist and beta-blocker none or at stable dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with an unplanned cardiac hospitalization or death due to a cardiac event
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2016 (estimated)
- Study startFeb 2016
- Primary completionDec 2025 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Martin Huelsmann
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Martin Huelsmann, Medical University of Vienna
- Investigators
- Martin Huelsmann, Doz.Dr., Principal investigator, Univ.Clinic II, Medical University Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02817360
- Sponsor's protocol ID
- PONTIAC II
- Status last verified
- Mar 2023
- First submitted
- 15 Feb 2016
- Last updated
- 14 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02817360
- Acronym / sponsor ID
- PONTIAC II
- Conditions
- Heart Diseases, Diabetes Mellitus, Type 2
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2,400 participants (estimated)
- Lead sponsor
- Martin HuelsmannUniversity, hospital or other
- Study start
- Feb 2016
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 29 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
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 objective 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).
Population The study population will consist of patients with T2DM without any history or signs of cardiac disease. Patients from approximately 20 centers worldwide will be included into the study and randomized 1:1 to intensive or conventional therapy. It is estimated that about 3000 patients have to be screened In order to include 2400 patients. The screen failure rate is anticipated to be approximately 20%.
Investigational and reference therapy All eligible patients will be randomized to receive either a high dose of RAS-antagonists and beta-blockers (as defined in the section investigational drugs) on top of standard diabetes therapy or solely standard diabetes therapy. The use of RAS-antagonist and beta-blocker therapy at randomization is allowed in the control group (with the exception of maximal dosage), but prescription or titration during the study period is not encouraged. However, if the investigators feel that further prescription or up-titration is required a thorough justification is mandatory. Every attempt should be made to use other blood pressure lowering drugs than RAS-antagonists or beta-blockers in the control group.
Study design This study is a randomized open-label, parallel group, active-controlled, two-arm, long-term morbidity and mortality trial to evaluate the efficacy and safety of high dose RAS-antagonist and beta-blocker therapy (as defined in the section investigational drugs) compared to standard diabetes therapy in patients with diabetes without any history or sign of a cardiac disease.
The goal is to include 2400 patients. The observation period is planned to last for two years. However, the trial is event driven and will continue until predefined event rate is reached. The total trial duration is expected to last for four years (two years of recruitment and a two year observation period after last patient in). Every patient will remain in the study for two years after randomization.
Visit 1 Screening At the first visit eligibility to enter the study will be assessed by the investigator. All inclusion/exclusion criteria will be evaluated. Informed consent will be obtained. Demographic data and drug prescription will be assessed. Blood will be obtained. Blood chemistry will be assessed locally. NT-proBNP will be determined by a point of care system locally. The investigator will be blinded to the result, which will be sent to the central computer. Blood will be obtained for the core lab, centrifuged and stored at -80° Celsius at the local unit. Vital signs will be obtained. Randomization will be performed electronically, this way randomization can be performed immediately.
Visit 2 (3 months) At visit 2 vital signs will be obtained. Blood will be drawn. Blood chemistry parameters will be assessed locally for safety reason. Drug prescription will be documented.
Visit 3 (12 months) At visit 3 vital signs will be obtained. Blood will be drawn. Blood chemistry parameters will be assessed locally for safety reason. Drug prescription will be documented.
Visit 4 EOS (end of study) (24 months) At visit 4 vital signs will be obtained. Blood will be drawn. Blood chemistry parameters will be assessed locally for safety reason. Additional blood samples will be sent to the core laboratory. Drug prescription will be documented.
Visit 1-4 is mandatory for all patients. Long-term follow-up Patients with be further followed by population register or telephone contact respectively until completion of the study to determine long-term mortality and hospitalizations.
Unscheduled visits for the treatment group The treatment group will have additional visits for up-titration of RAS-antagonists and beta- blocker between visit 1 and visit 2. The frequency is up to the treating physician and dependent on the titration steps. A visit is not mandatory for each titration step. Patients will receive a logbook by the investigator, with weekly up- titration steps of the drugs. Additionally, patients will receive a diary for daily documentation of blood pressure, heart rate and symptoms if measurement is technically feasible for the patient. Based on own measurements, these data and laboratory results the investigator will decide if further up-titration of medication is possible. Systolic blood pressure should not decrease permanently below 100 mmHg and heart not below 60bpm permanently. Recommended drugs and recommended dosages are outlined in the section "Treatment". At each visit, blood chemistry for eGFR, creatinine, blood urea nitrogen (BUN), sodium and potassium will be obtained for safety reason.
Details of the eye-substudy:
The PONTIAC Eye Study is a masked longitudinal follow up of previously 1:1 randomized study patients participating in the PONTIAC 2 study. It is planed to include 130 consecutive patients for biannually visits over a study period of 2 years. Study patients (n=130) will be assigned to the Department of Ophthalmology and Optometry of the Medical University Vienna once they are included in the PONTIAC 2 Study in one of the participating Centers in Vienna. The investigators will be masked to the patient's randomization.
The primary objective of the sub-study is: Superiority of the treatment arm with RAS-antagonists and beta-blockers compared to conventional therapy regarding thickness-change in the retinal nerve fiber layer or outer nuclear layer measured in spectral domain optical coherence tomography.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intensive therapy | Experimental | Drug: RAS-antagonist and beta-blocker up-to maximal dosagesRAS-antagonist and beta-blocker up-to maximal dosages as permitted and tolerated and following national guidelines. |
| Conventional therapy | Other | Other: RAS-antagonist and beta-blocker none or at stable doseNo 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Type-2 diabetes 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.
- Participation in the PONTIAC 2 Study
- Written informed consent to participate in the eye-study
Key exclusion criteria (28 listed)
- 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.
- Patients already on maximum dose of RAS-antagonist or beta-blocker.
- Creatinine > 2.5mg/dl.
- Symptomatic hypotension and/or systolic blood pressure (SBP) < 100 mmHg at Visit 1.
- Symptomatic bradycardia and/or heart rate (HR) < 60 bpm at Visit 1
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RAS-antagonist and beta-blocker up-to maximal dosagesAlso: Enalapril 40mg/d, Ramipril 10mg/d, Lisinopril 40mg/d, Cilazapril 5mg/dAll 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. | Drug | Intensive therapy |
| RAS-antagonist and beta-blocker none or at stable doseAll 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. | Other | Conventional therapy |
Primary outcome
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Martin Huelsmann, Doz.Dr. principal investigator
Univ.Clinic II, Medical University Vienna
21 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing RAS-antagonist and beta-blocker up-to maximal dosages and RAS-antagonist and beta-blocker none or at stable dose in people with Heart Diseases and Diabetes Mellitus, Type 2, run by Martin Huelsmann at 21 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Austria, United Kingdom, Spain, Netherlands, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Martin Huelsmann, Doz.Dr. (+43 1 40400 ext. 46140, martin.huelsmann@meduniwien.ac.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with an unplanned cardiac hospitalization or death due to a cardiac event (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2023.