TESTO-TRIAL: Use of Testosterone in Critically Ill Patients

NCT06592144 | Active Not Recruiting Phase 4

• 1 other identifier: CAAE76790723.5.0000.5440072024
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

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

Conditions

Weaning Failure; Muscle Weakness; Mechanical Ventilation Complication; ICU Acquired Weakness; Mobility Limitation

Keywords

Testosterone; Mechanical ventilation; Weaning; Critical Illness

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (20)

• Length of stay in the hospital, measured in days.

  ICU and hospital stay, assessed up to 8 weeks.

• Length of stay in the ICU, measured in days.

  ICU and hospital stay, assessed up to 8 weeks.

• Ventilator weaning time in days, starting from the date of randomization.

  ICU stay, assessed up to 8 weeks.

• In-hospital mortality from any cause.

  Hospital stay, assessed up to 8 weeks.

• Sequential Organ Failure Assessment (SOFA) score during the ICU stay, starting from the date of randomization.

  ICU stay, assessed up to 8 weeks.

Study Arms (2)

Testosterone

EXPERIMENTAL

Participants will receive 200 mg of testosterone cypionate intramuscularly every 5 days, up to a maximum of 3 doses.

Drug: Testosterone cypionate (200mg/3ml)

Sesame oil

PLACEBO COMPARATOR

Participants will receive sesame oil (placebo) intramuscularly every 5 days, up to a maximum of 3 doses.

Other: Sesame oil (3ml)

Interventions

Testosterone cypionate (200mg/3ml) DRUG

It will be administered intramuscularly every 5 days, totaling 3 doses.

Testosterone

Sesame oil (3ml) OTHER

It will be administered intramuscularly every 5 days, totaling 3 doses.

Sesame oil

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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;

Sponsors & Collaborators

• Leticia Maria Defendi Barboza Marson: lead

Study Sites (1)

Hospital Estadual Serrana

Serrana, SP/Brazil, 14150-000, Brazil

Location

Related Publications (14)

• 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.

  PMID: 32773614 BACKGROUND

• 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.

  PMID: 27272101 BACKGROUND

• 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.

  PMID: 35791659 BACKGROUND

• 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.

  PMID: 20592293 BACKGROUND

• 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.

  PMID: 29854477 BACKGROUND

• 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.

  PMID: 26454425 BACKGROUND

• 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.

  PMID: 29558983 BACKGROUND

• 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.

  PMID: 27620292 BACKGROUND

• 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.

  PMID: 35395861 BACKGROUND

• 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.

  PMID: 33237154 BACKGROUND

• 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.

  PMID: 35653254 BACKGROUND

• 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.

  PMID: 28386479 BACKGROUND

• 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.

  PMID: 26962061 BACKGROUND

• 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.

  PMID: 30591032 BACKGROUND

MeSH Terms

Conditions

Muscle Weakness; Mobility Limitation; Critical Illness

Interventions

testosterone 17 beta-cypionate; Sesame Oil

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fats, Unsaturated; Plant Oils; Oils; Plant Preparations; Biological Products; Complex Mixtures; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All assistant team members (physicians, pharmacists, nurses, etc.) and statisticians responsible for the analyses will remain blind to the identity of the treatments throughout the study. The placebo (sesame oil) will be prepared in a similar packaging and with a volume identical to that of testosterone cypionate. If a patient experiences an adverse effect potentially related to the medication, the attending physician may request to break the study blinding.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PhD student

Model Details: 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.

Study Record Dates

• First Submitted: August 27, 2024
• First Posted: September 19, 2024
• Study Start: September 9, 2024
• Primary Completion (Estimated): August 2, 2026
• Study Completion (Estimated): November 2, 2026
• Last Updated: December 18, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share

Locations

BR (1)