E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Woman and men suffering from heart failure NYHA II-IV and secondary pulmonary
hypertension
Objectives
PVR improvement after a 12 week oral Pentalong® therapy in addition to standard long-term HF medication as well as improvement on exercise capacity (6MWD),
quality of life (QOL-Questionaire), PAPsyst, LVEF, FS, TAPSE
(echocardiography) at rest, PCWP, PAPs, PAPd, PAPm, RAP, RVSD, RVEDP (right
heart catheter) at rest, biomarkers NTproBNP
|
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary objective: Superiority in PVR improvement after a 12 week oral Pentalong®
therapy in addition to standard long-term heart failure (HF) medication in patients suffering from HF |
|
E.2.2 | Secondary objectives of the trial |
Effects of Pentalong® therapy on exercise capacity (6MWD), quality of life (QOL Questionaire), PAPsyst, LVEF, FS, TAPSE (echocardiography) at rest, PCWP, PAPs, PAPd, PAPm, RAP, RVSD, RVEDP (right heart catheter) at rest, biomarkers NTproBNP (optional: Troponin-I, MR-proADM, CT-proET-1), optional Peak VO2 and VO2 at AT (CPET)
Optional Analyses of the effects on the total genomic expression profiles. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Written Informed Consent before randomization
- Men or women >18 and <80 years of age
- Documented clinically systolic HF (NYHA II-IV) and secondary pulmonary
hypertension
- PAPm >30mmHg, PCW >15 mmHg, LVEF <45%, TPG normal or elevated
- Ability of patient to understand the character and individual consequences of the
clinical trial
- For women with childbearing potential, adequate (Pearl Index <1) contraception. such as oral hormonal contraception (the pill), dermal hormonal contraception, vaginal hormonal contraception (NuvaRing), contraceptive patch, long-lasting injectable contraceptives, contraceptive coil, double barrier method) |
|
E.4 | Principal exclusion criteria |
- Cardiogenic shock
- Acute circulatory failure
- Acute decompensated heart failure (new occurrence of congestive signs)
- Myocarditis
- Implantation of CRT less than 12 months
- Listed for HTx on high urgency status
- Uncontrolled hypotension (systolic blood pressure <90 mmHg)
- Uncontrolled Hypertension (systolic blood pressure >200mmHg)
- Insufficient HF treatment not following ESC guidelines
- Not on stable treatment for at least three months
- Initiation of any of the following medications within the last 8 weeks: Aspirin,
statins, calcium channel blockers, ACE-inhibitors or AT-1 receptor blockers,
hormone replacement therapy.
- Use of phosphodiesterase-5-inhibitors (Viagra®, Revatio®, Cialis®, Levitra®),
dihydroergotamine and nitrates, i.e. isosorbidemononitrate, isosorbidedinitrate,
nitroglycerin, pentaerithrityltetranitrate, or molsidomin within the last two weeks.
- Treatment with hydralazin
- Hemodynamically significant aortic or mitral stenosis or hypertrophic obstructive
cardiomyopathy
- Renal dysfunction (creatinine > 2.5 mg/dl)
- Known hepatic disease (including hepatitis) or elevation of serum transaminases
or GT > 5x ULN (upper limit of normal range)
- Confirmed diagnosis of HIV infection
- WBC >16.000 or platelet count >500.000/μl or <75.000/μl
- Clinically overt hyperthyreodism
- Suspected hyperthyreodism
- Suspected Thyroid Carcinoma
- Febrile illnesses
- Known drug (alcohol) abuse
- Pregnancy and lactation
- Known intolerance to organic nitrates
- History of hypersensitivity to the investigational medicinal product or to any drug
with similar chemical structure or to any excipient present in the pharmaceutical
form of the investigational medicinal product
- X-ray contrast media allergy
- Other significant laboratory abnormalities that the investigator feels may
compromise the patient’s safety by participation in the study
- Participation in other clinical trials and observation period of competing trials,
respectively
- Intoxication
- Acute coronary syndrome
- Missing informed consent
No patient will be enrolled in this trial more than once. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
PVR improvement after a 12 week oral Pentalong® |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 16 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |