TESTO-TRIAL: Use of Testosterone in Critically Ill Patients (TT)

TESTO-TRIAL: Randomized Clinical Trial on the Use of Testosterone in Critically Ill Patients

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

Study Overview

• Status: Active, not recruiting
• Conditions: Muscle Weakness; Mechanical Ventilation Complication; Mobility Limitation; Weaning Failure; ICU Acquired Weakness
• Intervention / Treatment: Drug: Testosterone cypionate (200mg/3ml); Other: Sesame oil (3ml)

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 Type: Interventional
• Enrollment (Estimated): 94
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • SP/Brazil
    • Serrana, SP/Brazil, Brazil, 14150-000
      • Hospital Estadual Serrana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Testosterone; Participants will receive 200 mg of testosterone cypionate intramuscularly every 5 days, up to a maximum of 3 doses.	Drug: Testosterone cypionate (200mg/3ml); It will be administered intramuscularly every 5 days, totaling 3 doses.
Placebo Comparator: Sesame oil; Participants will receive sesame oil (placebo) intramuscularly every 5 days, up to a maximum of 3 doses.	Other: Sesame oil (3ml); It will be administered intramuscularly every 5 days, totaling 3 doses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilator-free days at 28 days, starting from the date of randomization.	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.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of stay in the hospital, measured in days.	Evaluate the effects of testosterone cypionate use on the length of hospital stays.	ICU and hospital stay, assessed up to 8 weeks.
Length of stay in the ICU, measured in days.	Evaluate the effects of testosterone cypionate use on the length of ICU (Intensive Care Unit) stays.	ICU and hospital stay, assessed up to 8 weeks.
Ventilator weaning time in days, starting from the date of randomization.	Evaluate the effects of testosterone cypionate use on the duration of mechanical ventilation.	ICU stay, assessed up to 8 weeks.
In-hospital mortality from any cause.	Evaluate the effects of testosterone cypionate use on in-hospital mortality.	Hospital stay, assessed up to 8 weeks.
Sequential Organ Failure Assessment (SOFA) score during the ICU stay, starting from the date of randomization.	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.	ICU stay, assessed up to 8 weeks.
Diaphragmatic muscle thickness.	Evaluate the effects of using testosterone cypionate on the diaphragmatic muscle during hospitalization by measuring diaphragm thickness (in millimeters) through ultrasonography.	Hospital stay, assessed up to 8 weeks
Diaphragmatic thickening fraction.	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.	Hospital stay, assessed up to 8 weeks
Skeletal muscle assessment: quadriceps thickness.	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.	Hospital stay, assessed up to 8 weeks.
Skeletal muscle assessment: Medical Research Council Sum-Score (MRC-SS).	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.	Hospital stay, assessed up to 8 weeks.
Skeletal muscle assessment: dynamometry.	Evaluate the effects of testosterone on muscle strength gain by measuring handgrip strength using dynamometry with the JAMAR dynamometer.	Hospital stay, assessed up to 8 weeks.
Skeletal muscle assessment: calf circumference.	Evaluate the effects of testosterone on muscle mass gain indirectly by measuring calf circumference (in centimeters).	Hospital stay, assessed up to 8 weeks.
Functionality and quality of life of critically ill patients during hospital stay: ICU Mobility Scale.	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).	Hospital stay, assessed up to 8 weeks.
Functionality and quality of life of critically ill patients during hospital stay: Perme Intensive Care Unit Mobility Score.	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.	Hospital stay, assessed up to 8 weeks.
Functionality and quality of life of critically ill patients during hospital stay: FSS-ICU (Functional Status Score for the Intensive Care Unit).	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).	Hospital stay, assessed up to 8 weeks.
Functionality and quality of life of critically ill patients during hospital stay: TUG (Timed Up and Go).	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.	Hospital stay, assessed up to 8 weeks.
Correlation of serum testosterone levels, clinical characteristics, and demographics of patients.	Evaluate the correlation between patients clinical and demographic characteristics, as well as free testosterone serum levels in the placebo and intervention groups.	Hospital stay, assessed up to 8 weeks.
Correlation with serum levels of hemoglobin and hematocrit, in addition to patients clinical characteristics.	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%).	Hospital stay, assessed up to 8 weeks.
Correlation with serum albumin levels and patients clinical characteristics.	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).	Hospital stay, assessed up to 8 weeks.
Functionality and quality of life of critically ill patients during hospital stay: the Barthel Index.	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.	Hospital stay, assessed up to 8 weeks.
Quality of life of critically ill patients during hospital stay: EQ-5D (EuroQol 5-Dimension).	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.	Hospital stay, assessed up to 8 weeks.

Collaborators and Investigators

• Sponsor: Leticia Maria Defendi Barboza Marson

Publications and helpful links

General Publications

• Zambon M, Greco M, Bocchino S, Cabrini L, Beccaria PF, Zangrillo A. Assessment of diaphragmatic dysfunction in the critically ill patient with ultrasound: a systematic review. Intensive Care Med. 2017 Jan;43(1):29-38. doi: 10.1007/s00134-016-4524-z. Epub 2016 Sep 12.
• Paris MT, Mourtzakis M, Day A, Leung R, Watharkar S, Kozar R, Earthman C, Kuchnia A, Dhaliwal R, Moisey L, Compher C, Martin N, Nicolo M, White T, Roosevelt H, Peterson S, Heyland DK. Validation of Bedside Ultrasound of Muscle Layer Thickness of the Quadriceps in the Critically Ill Patient (VALIDUM Study). JPEN J Parenter Enteral Nutr. 2017 Feb;41(2):171-180. doi: 10.1177/0148607116637852. Epub 2016 Jul 11.
• Santana PV, Cardenas LZ, Albuquerque ALP, Carvalho CRR, Caruso P. Diaphragmatic ultrasound: a review of its methodological aspects and clinical uses. J Bras Pneumol. 2020 Nov 20;46(6):e20200064. doi: 10.36416/1806-3756/e20200064. eCollection 2020.
• Wischmeyer PE, Suman OE, Kozar R, Wolf SE, Molinger J, Pastva AM. Role of anabolic testosterone agents and structured exercise to promote recovery in ICU survivors. Curr Opin Crit Care. 2020 Oct;26(5):508-515. doi: 10.1097/MCC.0000000000000757.
• Li H, Guo Y, Yang Z, Roy M, Guo Q. The efficacy and safety of oxandrolone treatment for patients with severe burns: A systematic review and meta-analysis. Burns. 2016 Jun;42(4):717-27. doi: 10.1016/j.burns.2015.08.023. Epub 2015 Oct 9.
• Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, Choong K, Lakshman KM, Mazer NA, Miciek R, Krasnoff J, Elmi A, Knapp PE, Brooks B, Appleman E, Aggarwal S, Bhasin G, Hede-Brierley L, Bhatia A, Collins L, LeBrasseur N, Fiore LD, Bhasin S. Adverse events associated with testosterone administration. N Engl J Med. 2010 Jul 8;363(2):109-22. doi: 10.1056/NEJMoa1000485. Epub 2010 Jun 30.
• Stanojcic M, Finnerty CC, Jeschke MG. Anabolic and anticatabolic agents in critical care. Curr Opin Crit Care. 2016 Aug;22(4):325-31. doi: 10.1097/MCC.0000000000000330.
• Anstey MH, Rauniyar R, Fitzclarence E, Tran N, Osnain E, Mammana B, Jacques A, Palmer RN, Chapman A, Wibrow B. Muscle Growth and Anabolism in Intensive Care Survivors (GAINS) trial: a pilot randomised controlled trial. Acute Crit Care. 2022 Aug;37(3):295-302. doi: 10.4266/acc.2021.01767. Epub 2022 Jun 27.
• Anstey M, Desai S, Torre L, Wibrow B, Seet J, Osnain E. Anabolic Steroid Use for Weight and Strength Gain in Critically Ill Patients: A Case Series and Review of the Literature. Case Rep Crit Care. 2018 May 7;2018:4545623. doi: 10.1155/2018/4545623. eCollection 2018.
• Dres M, Demoule A. Diaphragm dysfunction during weaning from mechanical ventilation: an underestimated phenomenon with clinical implications. Crit Care. 2018 Mar 20;22(1):73. doi: 10.1186/s13054-018-1992-2.
• Haaksma ME, Smit JM, Boussuges A, Demoule A, Dres M, Ferrari G, Formenti P, Goligher EC, Heunks L, Lim EHT, Mokkink LB, Soilemezi E, Shi Z, Umbrello M, Vetrugno L, Vivier E, Xu L, Zambon M, Tuinman PR. EXpert consensus On Diaphragm UltraSonography in the critically ill (EXODUS): a Delphi consensus statement on the measurement of diaphragm ultrasound-derived parameters in a critical care setting. Crit Care. 2022 Apr 8;26(1):99. doi: 10.1186/s13054-022-03975-5.
• Santangelo E, Mongodi S, Bouhemad B, Mojoli F. The weaning from mechanical ventilation: a comprehensive ultrasound approach. Curr Opin Crit Care. 2022 Jun 1;28(3):322-330. doi: 10.1097/MCC.0000000000000941.
• Galindo Martin CA, Monares Zepeda E, Lescas Mendez OA. Bedside Ultrasound Measurement of Rectus Femoris: A Tutorial for the Nutrition Support Clinician. J Nutr Metab. 2017;2017:2767232. doi: 10.1155/2017/2767232. Epub 2017 Mar 13.
• Pardo E, El Behi H, Boizeau P, Verdonk F, Alberti C, Lescot T. Reliability of ultrasound measurements of quadriceps muscle thickness in critically ill patients. BMC Anesthesiol. 2018 Dec 27;18(1):205. doi: 10.1186/s12871-018-0647-9.

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2024
• Primary Completion (Estimated): August 2, 2026
• Study Completion (Estimated): November 2, 2026

Study Registration Dates

• First Submitted: August 27, 2024
• First Submitted That Met QC Criteria: September 8, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Weaning; Critical Illness; Mechanical ventilation; Testosterone
• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Manifestations; Pathologic Processes; Muscle Weakness; Mobility Limitation; Asthenia; Antineoplastic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Anabolic Agents; Androgens; Methyltestosterone; Testosterone 17 beta-cypionate; Testosterone; Testosterone undecanoate; Testosterone enanthate
• Other Study ID Numbers: CAAE76790723.5.0000.5440072024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymous participant data will be available upon completion of clinical trials and publication of the results of the completed study upon request to the corresponding author. Proposals will be reviewed and approved by the sponsor, researcher, and staff on the basis of scientific merit and absence of competing interests. After the proposal has been approved, data can only be shared through a secure online platform after data access code exchange and a confidentiality agreement are signed.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No