Clinical trial • Phase IV • Endocrinology

TESTOSTERONE for Respiratory failure requiring invasive mechanical ventilation

Phase IV trial of TESTOSTERONE for Respiratory failure requiring invasive mechanical ventilation.

Overview

Trial Therapeutic Area
Endocrinology
Trial Disease
Respiratory failure requiring invasive mechanical ventilation
Trial Stage
Phase IV
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
28-11-2024
First CTIS Authorization Date
30-12-2024

Trial design

Randomised, placebo gel (testogel) versus androgel 16,2 mg/g gel (testosterone). androgel administered daily: 101.25 mg in men and 20.25 mg in women during the acute phase (treatment period up to 28 days); matching placebo gel used as comparator.-controlled Phase IV trial across 17 sites in France.

Randomised
Yes
Comparator
Placebo gel (TESTOGEL) versus ANDROGEL 16,2 mg/g gel (testosterone). ANDROGEL administered daily: 101.25 mg in men and 20.25 mg in women during the acute phase (treatment period up to 28 days); matching placebo gel used as comparator.
Target Sample Size
600
Trial Duration For Participant
365

Eligibility

Recruits 600 Vulnerable population: critically ill patients in ICU (isVulnerablePopulationSelected = true). Written informed consent must be obtained from the patient or the legal representative; subject information and informed consent forms for patients and for relatives/proxies are included among submitted documents (patient ICF and 'proche' / proxy ICF). Patients under legal guardianship are excluded and patients deprived of liberty are excluded..

Pregnancy Exclusion
Pregnancy
Vulnerable Population
Vulnerable population: critically ill patients in ICU (isVulnerablePopulationSelected = true). Written informed consent must be obtained from the patient or the legal representative; subject information and informed consent forms for patients and for relatives/proxies are included among submitted documents (patient ICF and 'proche' / proxy ICF). Patients under legal guardianship are excluded and patients deprived of liberty are excluded.

Inclusion criteria

  • {"criterion_text":"- Males and females aged over 18 years"}
  • {"criterion_text":"- Negative pregnancy test (b-HCG) in female patient of childbearing potential"}
  • {"criterion_text":"- COVID-19 or not"}
  • {"criterion_text":"- Patient on invasive mechanical ventilation for an expected total duration of at least 48 hours and still on invasive mechanical ventilation at the time of inclusion."}
  • {"criterion_text":"- Written informed consent obtained from the patient or the legal representative"}
  • {"criterion_text":"- Social security cover"}
  • {"criterion_text":"- Contraception : Female patient of childbearing potential (entering the study after a menstrual period and who has a negative pregnancy test), who agrees to use a highly effective method of contraception and an effective method of contraception by her male partner during treatment and for 7 months after the last treatment intake Male patient with a female partner of childbearing potential who agrees to use a highly effective method of contraception and an effective method of contraception by his female partner during treatment and for 4 months after the last treatment intake OR who agrees to use an effective method of contraception and a highly effective method of contraception by his female partner during the study and for 4 months after the last treatment intake"}

Exclusion criteria

  • {"criterion_text":"- History of prostate cancer"}
  • {"criterion_text":"- Breast feeding"}
  • {"criterion_text":"- Patients under legal guardianship"}
  • {"criterion_text":"- History of breast cancer"}
  • {"criterion_text":"- Prostate cancer suspected or confirmed"}
  • {"criterion_text":"- Breast cancer suspected or confirmed"}
  • {"criterion_text":"- PSA ≥ 4 ng/ml"}
  • {"criterion_text":"- ICU length of stay > 120 h before enrollment"}
  • {"criterion_text":"- Moribund"}
  • {"criterion_text":"- Pre-existing illness with a life expectancy of <6 months not connected to the acute pathology justifying ICU admission"}
  • {"criterion_text":"- Recent intracranial or spinal cord injury (< 1 month)"}
  • {"criterion_text":"- Recent hemorrhagic or ischemic stroke (< 1 month)"}
  • {"criterion_text":"- Language barrier"}
  • {"criterion_text":"- Patient deprived of liberty"}
  • {"criterion_text":"- Neuromuscular disease"}
  • {"criterion_text":"- Cardiac arrest in non-shockable rhythm"}
  • {"criterion_text":"- Pre-existing cognitive impairment with an MMS score < 20"}
  • {"criterion_text":"- Inability to walk without assistance prior to acute ICU illness (use of a cane or walkers not excluded)"}
  • {"criterion_text":"- Documented allergy to testosterone"}
  • {"criterion_text":"- Age > 80 years"}
  • {"criterion_text":"- Pregnancy"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- \tPhysical performance 3 months after ICU admission assessed by the 6-minute-walk distance test (6MWD) in metres. Absolute values will be compared to show a minimum absolute difference of 30 meters","definition_or_measurement_approach":"Assessed by the 6-minute-walk distance test (6MWD) in metres; absolute 6MWD values compared between arms with a minimum absolute difference of 30 metres"}

Secondary endpoints

  • {"endpoint_text":"- Physical performance 3, 6 months and 1 year after ICU admission : 6 MWD at 6 months and 1 year, Percentage of patients with Short Physical Performance Battery < 10 at 3, 6 months and 1 year, Physical component of SF 36 (Medical Outcomes Study 36 Item Short Form Health Survey) at 3, 6 months and 1 year","definition_or_measurement_approach":"6-minute walk distance (6MWD) at 6 months and 1 year; proportion with Short Physical Performance Battery < 10 at 3, 6, 12 months; SF-36 physical component at 3, 6, 12 months"}
  • {"endpoint_text":"- Muscle strength on ICU discharge at 3, 6 months and 1 year after ICU admission: - Handgrip: Kg and percentage of the predicted force, - MRC","definition_or_measurement_approach":"Handgrip strength measured in kg and as percent of predicted; MRC score at ICU discharge and at 3, 6, 12 months"}
  • {"endpoint_text":"- Muscle mass at 3, 6 and 1 year after ICU admission : MAMC","definition_or_measurement_approach":"Mid-arm muscle circumference (MAMC) measured at 3, 6, 12 months"}
  • {"endpoint_text":"- Functional status at 3, 6 months and 1 year after ICU admission : - Composite score of 11 items of ADL and IADL","definition_or_measurement_approach":"Composite score combining 11 items from ADL and IADL at 3, 6, 12 months"}
  • {"endpoint_text":"- Oxygen muscular consumption at ICU discharge and at 3 months after ICU admission","definition_or_measurement_approach":"Measurement of muscular oxygen consumption at ICU discharge and at 3 months"}
  • {"endpoint_text":"- Ventilation free days at day 28","definition_or_measurement_approach":"Number of ventilation-free days through day 28"}
  • {"endpoint_text":"- Length of stay in the ICU","definition_or_measurement_approach":"Duration (days) of ICU stay"}
  • {"endpoint_text":"- Length of stay in hospital","definition_or_measurement_approach":"Duration (days) of hospital stay"}
  • {"endpoint_text":"- Mortality rate at day 28","definition_or_measurement_approach":"All-cause mortality status at day 28 after ICU admission"}
  • {"endpoint_text":"- Mortality rate at day 90","definition_or_measurement_approach":"All-cause mortality status at day 90 after ICU admission"}
  • {"endpoint_text":"- ICU mortality rate","definition_or_measurement_approach":"All-cause mortality during ICU stay"}
  • {"endpoint_text":"- Hospital mortality rate","definition_or_measurement_approach":"All-cause mortality during hospital admission"}
  • {"endpoint_text":"- Safety of testosterone gel : - Hypertension, - Cardiovascular events, - Obstructive sleep apnea, - Increase in hemoglobin, hematocrit and red blood cells counts, - Alopecia, urticaria, acne, erythema, - Vertigo, paresthesia, - Depression, anxiety, - Gynaecomastia, - Oedema, weight gain, - insulin requirements, - Fractures","definition_or_measurement_approach":"Safety outcomes include monitoring and reporting of listed adverse events (hypertension, cardiovascular events, OSA, hematology changes, dermatologic events, neurological and psychiatric symptoms, gynaecomastia, oedema/weight gain, insulin requirements, fractures)"}

Recruitment

Planned Sample Size
600
Recruitment Window Months
48
Consent Approach
Written informed consent must be obtained from the patient or the legal representative. Subject information and informed consent forms (patient ICF, proxy/relative ICF and continuation/addendum versions) are included among submitted documents. No paediatric assent required (adults only). Submitted documents include French-language patient and proxy ICF versions.

Geography

Total Number Of Sites
17
Total Number Of Participants
600

France

Earliest CTIS Part Ii Submission Date
13-12-2024
Latest Decision Or Authorization Date
08-08-2025
Processing Time Days
238
Number Of Sites
17
Number Of Participants
600

Sites

Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Service d’Anesthésie et Réanimation
Principal Investigator Name
Samir JABER
Principal Investigator Email
s-jaber@chu-montpellier.fr
Contact Person Name
Samir JABER
Contact Person Email
s-jaber@chu-montpellier.fr
Site Name
Assistance Publique Hopitaux De Paris (Creteil)
Department Name
Service de Réanimation polyvalente
Principal Investigator Name
Armand MEKONTSO DESSAP
Principal Investigator Email
armand.dessap@aphp.fr
Contact Person Name
Armand MEKONTSO DESSAP
Contact Person Email
armand.dessap@aphp.fr
Site Name
Hospices Civils De Lyon
Department Name
Service de Médecine Intensive et Réanimation (MIR)
Principal Investigator Name
Laurent ARGAUD
Principal Investigator Email
laurent.argaud@chu-lyon.fr
Contact Person Name
Laurent ARGAUD
Contact Person Email
laurent.argaud@chu-lyon.fr
Site Name
Centre Hospitalier Universitaire De Montpellier (site 2)
Department Name
Service de Médecine Intensive et Réanimation (MIR)
Principal Investigator Name
Kada KLOUCHE
Principal Investigator Email
k-klouche@chu-chu-montpellier.fr
Contact Person Name
Kada KLOUCHE
Site Name
Assistance Publique Hopitaux De Paris (Garches)
Department Name
Service de Réanimation Médicale Adulte
Principal Investigator Name
Djillali ANNANE
Principal Investigator Email
djillali.annane@aphp.fr
Contact Person Name
Djillali ANNANE
Contact Person Email
djillali.annane@aphp.fr
Site Name
Centre Hospitalier VICHY
Department Name
Service de Réanimation
Principal Investigator Name
Ramin RAVIN
Principal Investigator Email
ramin.ravin@ch-vichy.fr
Contact Person Name
Ramin RAVIN
Contact Person Email
ramin.ravin@ch-vichy.fr
Site Name
Assistance Publique Hopitaux De Paris (Paris Cedex 18)
Department Name
Service de Médecine Intensive et Réanimation (MIR)
Principal Investigator Name
Jean-François TIMSIT
Principal Investigator Email
Jean-francois.timsit@bch.aphp.fr
Contact Person Name
Jean-François TIMSIT
Site Name
Centre Jean Perrin
Department Name
Service d’Anesthésie et Réanimation
Principal Investigator Name
Alexandre Lautrette
Principal Investigator Email
alautrette@chu-clermontferrand.fr
Contact Person Name
Alexandre Lautrette
Site Name
Hospices Civils De Lyon (Pierre Benite)
Department Name
Service d’Anesthésie et de Réanimation
Principal Investigator Name
Julien BOHE
Principal Investigator Email
julien.bohe@chu-lyon.fr
Contact Person Name
Julien BOHE
Contact Person Email
julien.bohe@chu-lyon.fr
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Service de Médecine Intensive et Réanimation (MIR)
Principal Investigator Name
Maëlle MARTIN
Principal Investigator Email
maelle.martin@chu-nantes.fr
Contact Person Name
Maëlle MARTIN
Contact Person Email
maelle.martin@chu-nantes.fr
Site Name
Centre Hospitalier Universitaire Grenoble Alpes
Department Name
Service de Médecine Intensive et Réanimation (MIR)
Principal Investigator Name
Anaïs DARTEVAL
Principal Investigator Email
adartevel@chu-grenoble.fr
Contact Person Name
Anaïs DARTEVAL
Contact Person Email
adartevel@chu-grenoble.fr
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Service de Réanimation polyvalente
Principal Investigator Name
Alexandre BOYER
Principal Investigator Email
alexandre.boyer@chu-bordeaux.fr
Contact Person Name
Alexandre BOYER
Site Name
Centre Hospitalier Departemental Vendee
Department Name
Service de Réanimation polyvalente
Principal Investigator Name
Konstantinos BACHOUMAS
Principal Investigator Email
konstantinos.bachoumas@chd-vendee.fr
Contact Person Name
Konstantinos BACHOUMAS
Site Name
University Hospital Of Clermont-Ferrand
Department Name
Service de Médecine Intensive et Réanimation (MIR)
Principal Investigator Name
Bertrand SOUWAINE
Principal Investigator Email
bsouweine@chu-clermontferrand.fr
Contact Person Name
Bertrand SOUWAINE
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Pôle Réanimation
Principal Investigator Name
Sébastien PREAU
Principal Investigator Email
sebastien.preau@chru-lille.fr
Contact Person Name
Sébastien PREAU
Contact Person Email
sebastien.preau@chru-lille.fr
Site Name
Assistance Publique Hopitaux De Paris (Paris)
Department Name
Service de Médecine Intensive et Réanimation (MIR)
Principal Investigator Name
Elie Azoulay
Principal Investigator Email
elie.azoulay@sls.aphp.fr
Contact Person Name
Elie Azoulay
Contact Person Email
elie.azoulay@sls.aphp.fr
Site Name
Hospices Civils De Lyon (Lyon Cedex 04)
Department Name
Service de Réanimation médicale
Principal Investigator Name
Jean-Christophe RICHARD
Principal Investigator Email
j-christophe.richard@chu-lyon.fr
Contact Person Name
Jean-Christophe RICHARD

Sponsor

Primary sponsor

Full Name
University Hospital Of Clermont-Ferrand
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
France

Investigational products

Investigational Product Name
ANDROGEL 16,2 mg/g, gel
Active Substance
TESTOSTERONE
Modality
Small molecule
Routes Of Administration
Cutaneous use (topical)
Route
Cutaneous use (topical gel)
Authorisation Status
Authorised (marketing authorisation in FR)
Starting Dose
101.25 mg (men); 20.25 mg (women)
Dose Levels
101.25 mg (men); 20.25 mg (women)
Frequency
Daily
Maximum Dose
101.25 mg/day
Investigational Product Name
TESTOGEL
Active Substance
PLACEBO
Modality
Other
Routes Of Administration
Cutaneous use (topical)
Route
Cutaneous use (topical gel)
Authorisation Status
Not authorised (investigational placebo)
Starting Dose
Matching placebo (dose matched to active: 101.25 mg men; 20.25 mg women)
Dose Levels
Same as active comparator (dose matched placebo)
Frequency
Daily
Maximum Dose
101.25 mg/day (placebo matched)

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