E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pulmonary Hypertension in Thalassaemia patients |
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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 |
To evaluate whether 12 weeks of treatment with oral sildenafil increases Six Minute Walk Time (6MWT) distance in thalassaemia patients with Pulmonary Hypertension (PHT).
Hypothesis: Mean twelve-week change in 6MWT distance will be greater than +60m in thalassaemia patients with PHT treated with oral sildenafil. |
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E.2.2 | Secondary objectives of the trial |
1) To evaluate whether 12 weeks of treatment with oral sildenail improves hemodynamics, pulmonary function and structure, hemolysis, arginine-nitric oxide dysregulation, hypercoagulability, inflammation, and cardiac load in thalassaemia patients with PHT.
2)To characterize PHT in thalassaemia with respect to exercise capacity, hemodynamics, pulmonary function and structure, hemolysis, arginine-nitric oxide dysregulation, hypercoagulability, inflammation, and cardiac load. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
INCLUSION CRITERIA
General: 1) Alpha, beta or E-beta thalassaemia confirmed by Hb-electrophoresis or molecular diagnosis 2) Age at entry at least 16 years
Intervention: 1) Pulmonary hypertension defined as TRjet velocity by Doppler echocardiography greater than 2.5 m/s
Control: 1) Lack of pulmonary hypertension defined as TRjet velocity by Doppler echocardiography less than 2.5 m/s
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E.4 | Principal exclusion criteria |
EXCLUSION CRITERIA 1) Pregnancy or lactation at baseline 2) Hypersensitivity to arginine or sildenafil based on prior use.
Any of the following medical conditions: - Severe renal insufficiency defined as use of hemodialysis or serum creatinine greater than 2.5mg/dl at the time of screening. - Cardiac disease with adjustment of cardiac medications within the last 60 days - Symptomatic coronary artery disease as indicated by a history of chest pain, angina, claudication or surgery to treat coronary artery disease within the last year - Stroke defined as a new focal neurological deficit lasting more than 24 hours within the last 45 days. - New diagnosis of pulmonary embolism by ventilation-perfusion scan, angiography or any other technique within the last 90 days - History of retinal detachment or retinal hemorrhage in the last 180 days - Use of nitrate-based vasodilators, prostacyclin (inhaled, subcutaneous or intravenous), endothelin antagonists, or any other medication for pulmonary hypertension. - Acute asthma exacerbation requiring use of prednisone within the last 60 days. - Initiation or dosage increase of calcium channel blockers within the last 30 days. - Initiation of any other cardiac or pulmonary medication within the last 90 days. - Patients with a TRjet velocity of exactly 2.5 are not eligible for either group. - Presence of any other condition, which in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the patient's compliance with the protocol, including but not limited to alcohol or drug abuse. - No measurable TRjet on Doppler echocardiography (i.e. presence of PHT cannot be confirmed or ruled out). - Inability or refusal to provide informed consent.
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E.5 End points |
E.5.1 | Primary end point(s) |
Changes in 6 Minute Walk Time (6MWT) distances will be calculated from each participant's baseline and will be analyzed in a linear model including time since treatment initiation and baseline 6MWT distance as fixed covariates and participant-specific intercepts as random terms. The primary outcome variable, 12-week change in 6MWT distance, will be estimated at the mean baseline 6MWT distance. |
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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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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 | Information not present in EudraCT |
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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Last clinic visit of the last subject enrolled in the study |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |