Effects of early testosterone gel administration on physical performance in the critically ill: a randomised double blind clinical trial.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Hospital Of Clermont-Ferrand

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

21 Jul 2023 → ongoing

Decision date (initial)

2024-12-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-519156-93-00

EudraCT number

2019-004599-20

ClinicalTrials.gov

NCT05825092

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To demonstrate that daily administration of testosterone gel, 101.25 mg in men and 20.25 mg in women, during the acute phase of critical illness, is more effective than placebo in improving physical performance 3 months after ICU admission.

Secondary objectives 12

1. To demonstrate that daily administration of testosterone gel 101.25 mg in men and 20.25 in women, during the acute phase of critical illness is more effective than placebo in improving physical performance 6 months and 1 year after ICU admission
2. To demonstrate that daily administration of testosterone gel 101.25 mg in men and 20.25 in women, during the acute phase of critical illness is more effective than placebo in increasing muscle strength at ICU discharge 3, 6 months and 1 year after ICU admission
3. To demonstrate that daily administration of testosterone gel 101.25 mg in men and 20.25 in women, during the acute phase of critical illness is more effective than placebo in improving functional status 3, 6 months and 1 year after ICU admission
4. To demonstrate that daily administration of testosterone gel 101.25 mg in men and 20.25 in women, during the acute phase of critical illness is more effective than placebo in improving oxygen muscular consumption at ICU discharge and at 3 months
5. To evaluate the impact of testosterone gel on the duration of invasive mechanical ventilation
6. To evaluate the impact of testosterone gel on the length of stay in the ICU
7. To evaluate the impact of testosterone gel on the length of stay in hospital
8. To evaluate the impact of testosterone gel on the mortality rate at 28 days after ICU admission
9. To evaluate the impact of testosterone gel on the mortality rate at 90 days after ICU admission
10. To evaluate the impact of testosterone gel on the hospital mortality rate
11. To evaluate the impact of testosterone gel on ICU mortality rate
12. To assess the safety of testosterone gel in critically ill patients

Conditions and MedDRA coding

Invasive mechanical ventilation expected to be required for more than 48 hours

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Males and females aged over 18 years
2. Negative pregnancy test (b-HCG) in female patient of childbearing potential
3. COVID-19 or not
4. 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.
5. Written informed consent obtained from the patient or the legal representative
6. Social security cover
7. 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 21

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. • Physical 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

Secondary endpoints 13

1. 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
2. Muscle strength on ICU discharge at 3, 6 months and 1 year after ICU admission: - Handgrip: Kg and percentage of the predicted force, - MRC
3. Muscle mass at 3, 6 and 1 year after ICU admission : MAMC
4. Functional status at 3, 6 months and 1 year after ICU admission : - Composite score of 11 items of ADL and IADL
5. Oxygen muscular consumption at ICU discharge and at 3 months after ICU admission
6. Ventilation free days at day 28
7. Length of stay in the ICU
8. Length of stay in hospital
9. Mortality rate at day 28
10. Mortality rate at day 90
11. ICU mortality rate
12. Hospital mortality rate
13. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Hospital Of Clermont-Ferrand

Sponsor organisation

University Hospital Of Clermont-Ferrand

Address

58 Rue Montalembert

City

Clermont Ferrand Cedex 1

Postcode

63003

Country

France

Scientific contact point

Organisation

University Hospital Of Clermont-Ferrand

Contact name

Lise Laclautre

Public contact point

Organisation

University Hospital Of Clermont-Ferrand

Contact name

Lise Laclautre

Locations

1 EU/EEA country · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications