E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neurogenic Orthostatic Hypotension (NOH) |
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E.1.1.1 | Medical condition in easily understood language |
Neurogenic Orthostatic Hypotension (NOH) |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10031127 |
E.1.2 | Term | Orthostatic hypotension |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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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 |
To evaluate the efficacy of a 4-week treatment with fludrocortisone (FLU) at stable dose on the decrease of systolic and diastolic blood pressure after 5 minutes of active orthostatism, in patients with neurogenic orthostatic hypotension |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the efficient dose of FLU to control NOH - To evaluate the effect of FLU on systolic blood pressure in supine and stand-up positions - To evaluate the effect of FLU on systolic blood pressure (BP) in supine and stand-up positions - To evaluate the effect of a treatment with FLU on prevalance and severity of the symptoms related to NOH - To evaluate the full responders rate (no symptoms and BP decrease <20 and/or 10 mmHg for systolic and diastolic values respectively) or partial responders rate (no symptoms but persistance of BP decrease) during treatment with FLU - To evaluate the effect of the treatment on nocturnal decubitus BP - To evaluate the effect of the treatment on left ventricular mass and ejection fraction on cardiac ultrasound - To evaluate the safety (adverse events) of FLU in the studied indication - To evaluate the effect of the treatment on the quality of life |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >18 years - Orthostatic hypotension (blodo pressure decrease >20 and/or 10mmHg on systolic and diastolic values within 3 minutes after stand-up, and symptomatic according to the Orthostatic Hypotension Questionnaire OHQ: score different than 0 in at least 1 of the 6 items - Patients suffering from a neurologic disease (Parkinson disease, multisystemic atrophy, Lewy bodies dementia, isolated progressive dysautonomia) or metabolic disease (diabetes, renal failure) known to be linked with an autonomous nervous system dysfunction and with NOH - Persistant and symptomatic NOH despite the use of non-medicinal measures (lower limbs contention) and medicinal products (midodrine) |
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E.4 | Principal exclusion criteria |
- Age <18 years - Hypersensitivity to FLU or to one of its excipients - Medical history of documented cardiac failure - Medical history of left ventricular systolic dysfunction - Non-compensated hypokalaemia - Nocturnal or supine hypertension - Pregnant or breastfeeding patients |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy on the systolic and diastolic BP decrease when moving from supine and stand-up position |
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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) |
Evaluation of the symptoms related to NOH through the OHQ scale Evaluation of the quality of life through the SF36 scale Collection of clinical adverse events, biological and blood pressure anomalies. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
OHQ scale and safety endpoints at each scheduled visit SF36 scale at screening visit and at the end of the double blind period |
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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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | No |
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
| 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 | 4 |
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 | No |
E.8.7 | Trial has a data monitoring committee | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |