E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008908 |
E.1.2 | Term | Chronic heart failure |
E.1.2 | System Organ Class | 100000004849 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective of the study is to evaluate the effect of sildenafil versus placebo on five main efficacy parameters which include patient global assessment and the 6 minute walk test. Significant improvements in these two parameters would constitute a positive trial. |
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E.2.2 | Secondary objectives of the trial |
Secondary, the study will evaluate the effect of sildenafil on selected biomarkers, renal function and systolic pulmonary arterial pressure. Secondary objectives would also include the safety and tolerability of sildenafil in the proposed patient population. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men and women
2. 18 – 80 years of age.
3. Outpatients with chronic HF. NYHA class III
4. LVEF < 40%
5. SPAP >40mmHg using echocardiography
6. 6MWTD < 475 meters
7. NT-pro BNP > 400 pg/ml on optimal treatment in sinus rhythm or atrial fibrillation
8. Receiving optimal therapy, including diuretic, ACE-inhibitor, ARB, beta-blocker and aldosterone antagonist. Doses of all medication should be unchanged during the last 30 days before inclusion.
9. ICDs and CRTs (CRT-P, CRT-D) are permitted. Implantation should have been performed at > 3 months before inclusion to the trial.
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E.4 | Principal exclusion criteria |
1. Acute Coronary Syndrome, including myocardial infarction, or coronary angiography, with or without intervention, within the last 3 months
2. Stroke within the last 3 months
3. Planned coronary angiography or planned device-implantation
4. Moderate to severe obstructive valve disease
5. Documented episodes of sustained ventricular tachycardia
6. Prior or ongoing use of oral nitrate therapy or frequent use of sublingual nitrate
7. Concomitant disease which interfere with assessment of dyspnoea , severe COPD, asthma, restrictive lung disease, severe obesity
8. Anemia (hemoglobin < 10g/dL)
9. Uncontrolled hypertension ( SBP >160 mmHg and / or DBP > 90 mmHg)
10. Symptomatic or orthostatic hypotension or systolic blood pressure < 90 mmHg
11. Clinically important renal dysfunction (GFR < 40m ml/min)
12. Women with child-bearing potential
13. Prior or ongoing use of
i) alpha-1 antagonist: doxazosin
ii) CYP3A4 inhibitors: erytromycin, ritonavir, sakinovir, itrakonazole, ketokonazole
iii) CYP3A4-inducers: rifampicin
14. Retinitis pigmentosa, previous diagnosis of NAION (non-arteritic ischemic opticus-neuropathy), unexplained visual disturbance.
15. Sickle cell anemia, multiple myeloma, leukemia or penile anatomic deformities (angulation, cavernosal fibrosis, Peyronie`s disease) that increases the risk of priapism.
16. Hepatic failure.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Patient global assessment (PGA).
2. 6 minute walk distance
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. EuroQoL5D
2. Kansas City Cardiomyopathy Questionnaire
3. NYHA function class
4. Renal function (serum creatinin and eGFR)
5. Systolic pulmonary arterial pressure
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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
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All participants will be followed on treatment for 6 months, and with an additional safety visit at 3 months following the termination of the study drug. |
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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 | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |