E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
- Hypermetabolism in ICU, loss of muscle mass and functional disability after ICU
- ICU acquired hypogonadism
- Treatment with testosterone gel in ICU
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E.1.1.1 | Medical condition in easily understood language |
- Hypermetabolism in ICU, loss of muscle mass and functional disability after ICU
- ICU acquired hypogonadism
- Treatment with testosterone gel in ICU
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
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 demonstrate that administration of 101.25 mg/day of testosterone gel in men and 20.25 mg/day in women, during the acute phase of critical illness, can restore normal serum values of total testosterone from day 4 to day 14. |
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E.2.2 | Secondary objectives of the trial |
• Proportion of patients with median free testosterone serum values at day 4, 7, 10, 14 higher than 58 pg/ml in men and 0,9 ng/ml in women
• Proportion of patients with median serum values of bioavailable testosterone at day 4, 7, 10, 14 higher than 75 ng/dl in men 0.8 ng/dl in women
• Safety of testosterone gel
• Daily and cumulative nitrogen balance from day 1 to extubation
• Physical performance at ICU discharge, 1month and 3 months after ICU discharge
• Muscle strength at ICU discharge, 1month and 3 months after ICU discharge
• Near Infrared Spectroscopy (NIRS) at ICU discharge
• Muscular mass at ICU discharge and one month after ICU discharge
• Lung function at 1 and 3 months after ICU discharge
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Males and females aged over 18 years receiving invasive mechanical ventilation
- Invasive mechanical ventilation expected to be required for more than 48 hours
- Treatment with vasoactive drugs
- Written informed consent obtained from the legal representative
- Social security cover
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E.4 | Principal exclusion criteria |
• History of prostate or breast cancer, prostatic specific antigen (PSA) ≥ 4 ng/ml
• ICU length of stay > 72 h before enrollment
• Moribund defined as having a score SAPS II > 75 12 hours after admission
• Pre-existing illness with a life expectancy of <6 months
• Cardiac arrest
• Preexistent cognitive impairment or language barrier
• Acute intracranial or spinal cord injury
• Acute hemorrhagic or ischemic stroke
• Neuromuscular disease (Guillain-Barré, myasthenia)
• Inability to walk without assistance prior to acute ICU illness (use of a cane or walkers not excluded)
• Documented allergy to testosterone
• Age > 80 years
• Pregnancy or breast feeding
• Patient under legal guardianship
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E.5 End points |
E.5.1 | Primary end point(s) |
• Proportion of patients with median value of serum total testosterone collected from blood samples at day 4, 7, 10, 14 higher than 280 ng/dl in men and 12 ng/dl in women. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
from day 4 to day 14 after inclusion |
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E.5.2 | Secondary end point(s) |
• Proportion of patients with median free testosterone serum values at day 4, 7, 10, 14 higher than 58 pg/ml in men and 0,9 ng/ml in women
• Proportion of patients with median serum values of bioavailable testosterone at day 4, 7, 10, 14 higher than 75 ng/dl in men 0.8 ng/dl in women
• Safety of testosterone gel
• Daily and cumulative nitrogen balance from day 1 to extubation
• Physical performance at ICU discharge, 1month and 3 months after ICU discharge
• Muscle strength at ICU discharge, 1month and 3 months after ICU discharge
• Near Infrared Spectroscopy (NIRS) at ICU discharge
• Muscular mass at ICU discharge and one month after ICU discharge
• Lung function at 1 and 3 months after ICU discharge
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at day 4, 7, 10, 14 higher than 58 pg/ml in men and 0,9 ng/ml in women
• Proportion of patients with median serum values of bioavailable testosterone
• throughout the duration of the study
• day 1 to extubation
• at ICU discharge, 1month and 3 months after ICU discharge
• at ICU discharge, 1month and 3 months after ICU discharge
at ICU discharge
• at ICU discharge and one month after ICU discharge
• at 1 and 3 months after ICU discharge
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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 | No |
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) | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
In the control group, AndroGel will not be administered. |
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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 | 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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The duration of the study extends from the inclusion until 3 months after ICU discharge.
The study will be interrupted for the following reasons:
• Withdrawal of consent: when a subject withdraws consent before completing the study, the reason for withdrawal of consent is to be documented on the eCRF and in the source document.
• Adverse experiences
• At the request of the investigator or sponsor, whether for administrative or other reasons
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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 | |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | |