Clinical trial NCT06592144: TESTO-TRIAL: Use of Testosterone in Critically Ill Patients
Official title: TESTO-TRIAL: Randomized Clinical Trial on the Use of Testosterone in Critically Ill Patients
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Weaning Failure
Muscle Weakness
Mechanical Ventilation Complication
ICU Acquired Weakness
Mobility Limitation
Keywords: Testosterone
Mechanical ventilation
Weaning
Critical Illness
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
First posted: 2024-09-19
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Intervention Group: Participants will receive 200 mg of testosterone cypionate intramuscularly every 5 days, up to a maximum of 3 doses.

Control Group: Participants will receive sesame oil (placebo) intramuscularly every 5 days, up to a maximum of 3 doses.
Primary purpose: SUPPORTIVE_CARE

Brief summary: The objective of this study is to evaluate whether the use of the anabolic agent testosterone cypionate in critically ill patients, compared to placebo, increases the number of ventilator-free days

Detailed description: It will be a randomized, controlled, double-blind, single-center clinical trial conducted in the Intensive Care Unit (ICU) of the State Hospital of Serrana (HE Serrana). Patients admitted to the ICU who meet the eligibility criteria and have given written informed consent will be randomized into control and intervention groups. Forty-seven patients will be included in each group, totaling 94 patients. The intervention group will receive 200 mg of testosterone cypionate intramuscularly every 5 days for a total of 3 doses. The control group will receive a placebo on the same schedule. After inclusion in the study, demographic and clinical data, laboratory results, ultrasonographic measurements, and functionality and muscle strength scores will be assessed on days 1, 5, 10, and 15 in the ICU and until hospital discharge.

Eligibility criteria: Inclusion Criteria:

* Patients on mechanical ventilation (MV) for seven days or more, or patients on MV with an unsuccessful weaning attempt for at least three days. An unsuccessful weaning attempt is defined as the patient undergoing a Spontaneous Breathing Trial (SBT) on three different days without success, according to the ICU protocol;
* Over 18 years old;
* Patients with optimized nutritional therapy, defined by caloric and protein goals met for at least three days;
* Signing the informed consent form (ICF).

Exclusion Criteria:

* Hypersensitivity to the medication, the vehicle of the medication, or the placebo (sesame oil);
* Venous or arterial thrombosis in the past six months, including acute myocardial infarction, ischemic stroke, acute arterial occlusion, mesenteric ischemia, venous thromboembolism, or pulmonary embolism;
* Left Ventricular Ejection Fraction (LVEF) below 35%;
* Glutamic-pyruvic transaminase/Alanine Aminotransferase (GPT/ALT) greater than five times the normal level and impaired bilirubin excretion;
* Patients with liver cirrhosis (CHILD \> B);
* Pregnant or lactating women;
* Women of childbearing age;
* Hematocrit \>52%;
* Refractory shock, defined as requiring a norepinephrine dose \> 0.5 mcg/kg/min or a vasopressin dose \> 0.04 IU/min;
* Thrombocytopenia \< 20,000/mm³ without a transfusion plan;
* Personal history of prostate or breast cancer;
* Active neoplasm of any site;
* Primary neuromuscular disease, including Amyotrophic Lateral Sclerosis (ALS), Duchenne muscular dystrophy, myasthenia gravis, or Guillain-Barré syndrome;
* Current or previous spinal cord injury above C4 (tetraplegia);
* Patients with total limitation of therapeutic measures;

Primary outcomes:
measure: Ventilator-free days at 28 days, starting from the date of randomization.
timeFrame: 28 days
Secondary outcomes:
measure: Length of stay in the hospital, measured in days.
timeFrame: ICU and hospital stay, assessed up to 8 weeks.
measure: Length of stay in the ICU, measured in days.
timeFrame: ICU and hospital stay, assessed up to 8 weeks.
measure: Ventilator weaning time in days, starting from the date of randomization.
timeFrame: ICU stay, assessed up to 8 weeks.
measure: In-hospital mortality from any cause.
timeFrame: Hospital stay, assessed up to 8 weeks.
measure: Sequential Organ Failure Assessment (SOFA) score during the ICU stay, starting from the date of randomization.
timeFrame: ICU stay, assessed up to 8 weeks.
measure: Diaphragmatic muscle thickness.
timeFrame: Hospital stay, assessed up to 8 weeks
measure: Diaphragmatic thickening fraction.
timeFrame: Hospital stay, assessed up to 8 weeks
measure: Skeletal muscle assessment: quadriceps thickness.
timeFrame: Hospital stay, assessed up to 8 weeks.
measure: Skeletal muscle assessment: Medical Research Council Sum-Score (MRC-SS).
timeFrame: Hospital stay, assessed up to 8 weeks.
measure: Skeletal muscle assessment: dynamometry.
timeFrame: Hospital stay, assessed up to 8 weeks.
measure: Skeletal muscle assessment: calf circumference.
timeFrame: Hospital stay, assessed up to 8 weeks.
measure: Functionality and quality of life of critically ill patients during hospital stay: ICU Mobility Scale.
timeFrame: Hospital stay, assessed up to 8 weeks.
measure: Functionality and quality of life of critically ill patients during hospital stay: Perme Intensive Care Unit Mobility Score.
timeFrame: Hospital stay, assessed up to 8 weeks.
measure: Functionality and quality of life of critically ill patients during hospital stay: FSS-ICU (Functional Status Score for the Intensive Care Unit).
timeFrame: Hospital stay, assessed up to 8 weeks.
measure: Functionality and quality of life of critically ill patients during hospital stay: TUG (Timed Up and Go).
timeFrame: Hospital stay, assessed up to 8 weeks.
measure: Correlation of serum testosterone levels, clinical characteristics, and demographics of patients.
timeFrame: Hospital stay, assessed up to 8 weeks.
measure: Correlation with serum levels of hemoglobin and hematocrit, in addition to patients clinical characteristics.
timeFrame: Hospital stay, assessed up to 8 weeks.
measure: Correlation with serum albumin levels and patients clinical characteristics.
timeFrame: Hospital stay, assessed up to 8 weeks.
measure: Functionality and quality of life of critically ill patients during hospital stay: the Barthel Index.
timeFrame: Hospital stay, assessed up to 8 weeks.
measure: Quality of life of critically ill patients during hospital stay: EQ-5D (EuroQol 5-Dimension).
timeFrame: Hospital stay, assessed up to 8 weeks.
Other outcomes:
Locations:
city: Serrana
country: Brazil
facility: Hospital Estadual Serrana
state: SP/Brazil
Study officials:
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