Brief Summary

Critically ill patients experience major insults that lead to increased protein catabolism. Hypermetabolism occurs early and rapidly during the first week of critical illness to provide amino acids for the production of energy via gluconeogenesis, and also for the synthesis of acute phase proteins and repair of tissue damage. During acute phase, neuroendocrine and inflammatory responses promote protein breakdown and amino acid release. Under stress conditions, protein synthesis cannot match the increased rate of muscle proteolysis because of a state of anabolism resistance, which limits uptake of amino acids into muscles. Hypermetabolism results in a significant loss of lean body mass with an impact on weaning from the ventilator and muscle recovery. Functional disability can be long term sometimes with no full return to normal. In critically ill patients, severe and persistent testosterone deficiency is very common and is observed early after Intensive Care Unit (ICU) admission. This acquired hypogonadism promotes the persistent loss of skeletal muscle protein and is related to poor outcome. Administration of testosterone induces skeletal muscle fiber hypertrophy and decreases protein breakdown in healthy young men. It has been repeatedly shown that testosterone treatment enhances muscle mass and strength in hypogonadal men and women and can improve physical performance. Testosterone administration in burned patients reduces protein breakdown and increases protein synthesis efficiency. Oxandrolone, a synthetic testosterone analogue, reduces body mass and nitrogen loss and accelerates healing in burned patients. Trials in critically ill unburned patients failed to demonstrate any effect on clinical outcome but the studies were underpowered to detect a difference. Transdermal gel testosterone is the preferred route of administration for achieving steady serum testosterone concentrations as compared to oral and intramuscular formulations. Intramuscular injection induces strong fluctuations of testosterone plasma concentrations and can cause haematoma in patients with coagulation disorders, a common condition in ICUs. Several studies have raised the concern that testosterone administration could increase the risk of cardiovascular disease events. However, in a recent meta-analysis, no significant effects on cardiovascular risk were observed with either injected or transdermal testosterone supplementation in men, and the French National Agency for Medicines (ANSM) recently reported that drugs containing testosterone were not associated with an increased risk of cardiovascular events.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

600

participants targeted

Target at P75+ for phase_2

Timeline

11mo left

Started Jul 2023

Typical duration for phase_2

Geographic Reach

1 country

5 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

3.7 years study duration

Study Progress76%

Jul 2023Apr 2027

First Submitted

Initial submission to the registry

November 30, 2022

Completed

5 months until next milestone

First Posted

Study publicly available on registry

April 24, 2023

Completed

3 months until next milestone

Study Start

First participant enrolled

July 21, 2023

Completed

2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2025

Completed

1.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2027

Expected

Last Updated

October 2, 2023

Status Verified

April 1, 2023

Enrollment Period

2.1 years

First QC Date

November 30, 2022

Last Update Submit

September 29, 2023

Conditions

Critical Illness

Keywords

Critical ill patientPhysical performanceTestosterone

Outcome Measures

Primary Outcomes (1)

the 6-minute-walk distance test (6MWD)
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
3 months after ICU admission

Secondary Outcomes (17)

the 6-minute-walk
6 months
the 6-minute-walk
1 year after ICU admission
Functional status with Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL)
at 3, 6 months and 1 year after ICU admission
Oxygen muscular consumption with NIRS test (Near Infrared Spectroscopy)
48 hours after intensive care unit (ICU) admission and 3 months after ICU admission
Muscular mass with MAMC (Mid-arm muscle circumference):
at 3, 6 months and 1 year after ICU admission
+12 more secondary outcomes

Study Arms (2)

AndroGel® 1.62%

ACTIVE COMPARATOR

AndroGel® will be applied daily to the upper arms/shoulders. AndroGel® will be administered within 24 hours after inclusion for a period of 28 days or until hospital discharge. For patients discharged from ICU before day 28, AndroGel® will be administered in hospital wards to complete the 28 days of treatment or until hospital discharge

Drug: Androgel Topical ProductDiagnostic Test: Physical performanceDiagnostic Test: Muscle strengthDiagnostic Test: Muscular massDiagnostic Test: Test: Functional statusDiagnostic Test: Oxygen muscular consumption

Placebo gel will be the same gel without testosterone

PLACEBO COMPARATOR

Placebo gel will be applied daily to the upper arms/shoulders. Placebo gel will be administered within 24 hours after inclusion for a period of 28 days or until hospital discharge. For patients discharged from ICU before day 28, Placebo gel will be administered in hospital wards to complete the 28 days of treatment or until hospital discharge

Drug: PlaceboDiagnostic Test: Physical performanceDiagnostic Test: Muscle strengthDiagnostic Test: Muscular massDiagnostic Test: Test: Functional statusDiagnostic Test: Oxygen muscular consumption

Interventions

Androgel Topical ProductDRUG

AndroGel® will be applied daily to the upper arms/shoulders at 9:00 am. The daily dose will be 101.25 mg in men and 20.25 mg in women. AndroGel® will be administered within 24 hours after inclusion for a period of 28 days or until hospital discharge. For patients discharged from ICU before day 28, AndroGel® will be administered in hospital wards to complete the 28 days of treatment or until hospital discharge

Also known as: Androgel 1.62% Transdermal Gel

AndroGel® 1.62%

PlaceboDRUG

Placebo gel will be applied daily to the upper arms/shoulders at 9:00 am. The daily dose will be 101.25 mg in men and 20.25 mg in women. Placebo gel will be administered within 24 hours after inclusion for a period of 28 days or until hospital discharge. For patients discharged from ICU before day 28, Placebo gel will be administered in hospital wards to complete the 28 days of

Placebo gel will be the same gel without testosterone

Physical performanceDIAGNOSTIC_TEST

Physical performance at 3, 6 months and 1 year after ICU admission 6 minute walk distance 3 months after ICU admission, at 6 months and at 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