TESTO-TRIAL: Use of Testosterone in Critically Ill Patients

Phase 4

Active, not recruiting

• Conditions: Weaning Failure; Muscle Weakness; Mechanical Ventilation Complication; ICU Acquired Weakness; Mobility Limitation
• Interventions: Drug: Testosterone cypionate (200mg/3ml); Other: Sesame oil (3ml)

• Registration Number: NCT06592144
• Lead Sponsor: Leticia Maria Defendi Barboza Marson

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.

Study Timeline

• Study First Submitted: 2024-08-27
• Study First Submitted QC: 2024-09-08
• Study Start: 2024-09-09
• Study First Posted: 2024-09-19
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-13
• Last Update Posted: 2024-12-18
• Primary Completion: 2026-08-02
• Study Completion: 2026-11-02

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 94

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;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Testosterone	Testosterone cypionate (200mg/3ml)	Participants will receive 200 mg of testosterone cypionate intramuscularly every 5 days, up to a maximum of 3 doses.
Sesame oil	Sesame oil (3ml)	Participants will receive sesame oil (placebo) intramuscularly every 5 days, up to a maximum of 3 doses.

Primary Outcome Measures

Name	Time	Method
Ventilator-free days at 28 days, starting from the date of randomization.	28 days	Evaluate whether the use of the anabolic steroid testosterone cypionate, compared to a placebo, increases the number of ventilator-free days in critically ill patients.

Secondary Outcome Measures

Name	Time	Method
Functionality and quality of life of critically ill patients during hospital stay: ICU Mobility Scale.	Hospital stay, assessed up to 8 weeks.	Evaluate the effects of testosterone cypionate use on functionality scores, including the ICU Mobility Scale (IMS) to objectively measure the mobility of patients in the ICU. This scale has a score ranging from 0 to 10, where a score of zero indicates low mobility (interpreted as a patient who only performs passive bed exercises) and a score of 10 indicates high mobility (interpreted as a patient who is independently ambulatory, without assistance).
Functionality and quality of life of critically ill patients during hospital stay: Perme Intensive Care Unit Mobility Score.	Hospital stay, assessed up to 8 weeks.	Perme Intensive Care Unit Mobility Score objectively measures the mobility condition of a patient in the ICU. This mobility scale has a score ranging from 0 to 32 points, divided into 15 items grouped into 7 categories: mental state, potential barriers to mobility, functional strength, bed mobility, transfers, assistive devices for ambulation, and endurance measures. In this scale, a higher score indicates greater mobility and less need for assistance. Conversely, a lower score indicates reduced mobility and a greater need for assistance.
Functionality and quality of life of critically ill patients during hospital stay: FSS-ICU (Functional Status Score for the Intensive Care Unit).	Hospital stay, assessed up to 8 weeks.	Evaluate the effects of testosterone on the functionality of critically ill patients using the FSS-ICU, a tool that involves five functional tasks (rolling, transferring from supine to sitting, transferring from sitting to standing, sitting on the edge of the bed, and walking). Each task is assessed using an 8-point ordinal scale, ranging from 0 (completely unable to perform) to 7 (complete independence).
Functionality and quality of life of critically ill patients during hospital stay: TUG (Timed Up and Go).	Hospital stay, assessed up to 8 weeks.	Evaluate the effects of testosterone cypionate use on functionality scores, including the TUG (Timed Up and Go). The parameter evaluated is the time spent (in seconds) to rise from a chair, walk a distance of 3 meters, and return to sit down. The test is considered normal when the time taken is less than 10 seconds. If the time is between 10 and 19 seconds, the elderly person is considered to have a moderate risk of falling, and this risk increases when the time is 20 seconds or more.
Skeletal muscle assessment: Medical Research Council Sum-Score (MRC-SS).	Hospital stay, assessed up to 8 weeks.	Evaluate the effects of testosterone cypionate on muscle strength gain using the MRC, which scores muscle strength from 0 (no contraction) to 5 (normal muscle contraction) for shoulder flexors, elbow flexors, wrist extensors, hip flexors, knee extensors, and ankle dorsiflexors, totaling 60 points.
Skeletal muscle assessment: dynamometry.	Hospital stay, assessed up to 8 weeks.	Evaluate the effects of testosterone on muscle strength gain by measuring handgrip strength using dynamometry with the JAMAR dynamometer.
Skeletal muscle assessment: calf circumference.	Hospital stay, assessed up to 8 weeks.	Evaluate the effects of testosterone on muscle mass gain indirectly by measuring calf circumference (in centimeters).
Correlation of serum testosterone levels, clinical characteristics, and demographics of patients.	Hospital stay, assessed up to 8 weeks.	Evaluate the correlation between patients clinical and demographic characteristics, as well as free testosterone serum levels in the placebo and intervention groups.
Correlation with serum levels of hemoglobin and hematocrit, in addition to patients clinical characteristics.	Hospital stay, assessed up to 8 weeks.	Evaluate the correlation between patients clinical and demographic characteristics and laboratory test levels, about the use of testosterone and the stimulation of erythropoietin production, leading to an increase in red blood cell production and, consequently, an increase in hemoglobin (normal value: 12.5 to 17.2 g/dL) and hematocrit (37-49%).
Correlation with serum albumin levels and patients clinical characteristics.	Hospital stay, assessed up to 8 weeks.	Evaluate the correlation between patients clinical and demographic characteristics and laboratory test levels, considering the affinity of total testosterone to albumin (normal value: 3.2 to 4.8 g/dL).
Functionality and quality of life of critically ill patients during hospital stay: the Barthel Index.	Hospital stay, assessed up to 8 weeks.	Evaluate the effects of using testosterone cypionate on functionality scores, including the Barthel Index at hospital discharge. The Barthel Index consists of ten items, such as feeding, transferring from bed to chair and back, personal hygiene, using the toilet, bathing, walking on a flat surface, stairs, dressing, fecal continence, and bladder continence. Each item has variable scores ranging from zero to fifteen points, depending on the individuals level of functional dependence. The maximum score is 100, which is assigned only if the patient does not require any assistance.
Quality of life of critically ill patients during hospital stay: EQ-5D (EuroQol 5-Dimension).	Hospital stay, assessed up to 8 weeks.	Evaluate the effects of testosterone cypionate use on quality of life, including the EQ-5D (EuroQol 5-Dimension) at hospital discharge.; The EQ-5D includes five levels of response for each of the five variables assessed: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each variable is scored from 1 to 5, where 1 indicates no problems and 5 indicates extreme problems. The final score is a combination of the numbers assigned to each variable, resulting in a five-digit code that represents the patients health status.
Length of stay in the hospital, measured in days.	ICU and hospital stay, assessed up to 8 weeks.	Evaluate the effects of testosterone cypionate use on the length of hospital stays.
Length of stay in the ICU, measured in days.	ICU and hospital stay, assessed up to 8 weeks.	Evaluate the effects of testosterone cypionate use on the length of ICU (Intensive Care Unit) stays.
Ventilator weaning time in days, starting from the date of randomization.	ICU stay, assessed up to 8 weeks.	Evaluate the effects of testosterone cypionate use on the duration of mechanical ventilation.
In-hospital mortality from any cause.	Hospital stay, assessed up to 8 weeks.	Evaluate the effects of testosterone cypionate use on in-hospital mortality.
Sequential Organ Failure Assessment (SOFA) score during the ICU stay, starting from the date of randomization.	ICU stay, assessed up to 8 weeks.	Evaluate the effects of using testosterone cypionate on the SOFA score during ICU hospitalization. This score is used to assess the degree of organ dysfunction in the patient, with scores ranging from 0 to 24 points; the higher the score, the greater the severity and risk of mortality in critically ill patients.
Diaphragmatic muscle thickness.	Hospital stay, assessed up to 8 weeks	Evaluate the effects of using testosterone cypionate on the diaphragmatic muscle during hospitalization by measuring diaphragm thickness (in millimeters) through ultrasonography.
Diaphragmatic thickening fraction.	Hospital stay, assessed up to 8 weeks	Evaluate the effects of using testosterone cypionate on the diaphragmatic muscle during hospitalization through ultrasonography. The thickening fraction is calculated using the following equation: (Final inspiratory diaphragm thickness - Final expiratory diaphragm thickness)/Final expiratory diaphragm thickness × 100. If the result is greater than 36%, it predicts successful weaning from mechanical ventilation.
Skeletal muscle assessment: quadriceps thickness.	Hospital stay, assessed up to 8 weeks.	Evaluate the effects of using testosterone cypionate on the thickness of the rectus femoris muscle by measuring its thickness at maximum and minimum compression through ultrasonographic analysis.

Trial Locations

Locations (1)

Hospital Estadual Serrana; 🇧🇷 Serrana, SP/Brazil, Brazil