Role of Levothyroxine Supplementation in Delayed Recovery Following Cardiac Surgery

NCT06660823 | Completed Phase 3 Results DMC

• 1 other identifier: FMASU R237/2024
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Research indicates that hypothyroidism decreases heart contractility, reduces stroke volume and rate, affects the vascular endothelium, and increases the risk of atherosclerosis, systemic vascular resistance, hypertension, atherogenic lipid profile, and coagulation abnormality . Hypothyroidism was reported to be strongly related to cardiovascular disease, respiratory complications, neurological complications, and a significant difference in ventilator weaning time. Once subclinical hypothyroidism patients are treated with levothyroxine, their physical fitness measured by a 6-minute walk is significantly improved, also showed that levothyroxine treatment can optimize the treatment of heart failure with preserved functions (HFpEF) and heart failure with reduced functions (HFrEF) patients with systolic left ventricular dysfunction and sub clinical hypothyroidism (SCH). The primary aim of this study is to investigate the effect of supplementation of oral levothyroxine in delayed recovery patients post cardiac surgery.

Conditions

Cardiac Surgery Intensive Care Treatment; Delayed Recovery From Anaesthesia; Euthyroid Sick Syndrome; Cardiac Surgery Requiring Cardiopulmonary Bypass

Keywords

L-Thyroxine; Delayed recovery post cardiac surgery; hypthyroidism

Outcome Measures

Primary Outcomes (1)

• Change in Glasgow Coma Scale (GCS) From Intervention Initiation to ICU Discharge (Δ)

  The Glasgow Coma Scale (GCS) assesses conscious level through three components: Eye response (scored 1-4): 4: Opens eyes spontaneously 3: Opens eyes to verbal command 2: Opens eyes to pain 1: No eye opening Verbal response (scored 1-5): 5: Oriented and converses 4: Confused 3: Inappropriate words 2: Incomprehensible sounds 1: No verbal response Motor response (scored 1-6): 6: Obeys commands 5: Localizes to pain 4: Withdraws from pain 3: Abnormal flexion (decorticate) 2: Abnormal extension (decerebrate) 1: No motor response The total GCS score ranges from 3 (worst) to 15 (best), with higher scores indicating better neurological function. The primary outcome is the change in total GCS score from baseline (48 hours postoperatively, before intervention) to ICU discharge.

  From intervention initiation (48 hours postoperatively) to ICU discharge, up to 1 month postoperatively. (i.e., within 28 days after baseline).

Secondary Outcomes (6)

• Total Duration of Mechanical Ventilation

  From surgery completion until extubation (assessed for ≤30 days postoperatively).

• Duration of Intensive Care Unit (ICU) Stay

  From ICU admission until discharge/death (assessed for ≤30 days postoperatively).

• Total Hospital Stay Stay.

  30 days

• Average Inotropic Support Infusion Rate in ICU

  From ICU admission until discontinuation of inotropic support or ICU discharge (assessed daily for ≤30 days).

• Change in Left Ventricular Ejection Fraction (LVEF) From Baseline to ICU Discharge

  Preoperative assessment: Within 24 hours before surgery Postoperative assessment: At ICU discharge (≤30 days postoperatively)

Study Arms (2)

Group A (Study group)

ACTIVE COMPARATOR

group A will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI

Drug: L-thyroxine

Group B (Control)

PLACEBO COMPARATOR

group B will receive placebo in form of inert starch tablet

Drug: Placebo Oral Tablet

Interventions

L-thyroxine DRUG

Patients who show signs of delayed recovery defined as either prolonged ventilation for 48 hours or delayed conscious level recovery for 48 hours despite exclusion of muscle relaxants and/or sedative drugs. Those patients will undergo CT brain, CT chest and neurological examination to exclude structural damage as per institutional protocols. Also, metabolic profile screening including full kidney function, full liver function, electrolyte to exclude correctable metabolic abnormalities. and thyroid profile (TSH, free T3, free T4) sick euthyroid patients who are having normal FreeT3, normal Free T4, low TSH and low level of free T3 or freeT4 will be included in the study according lab reference.Daily assessment of conscious level according to Glasgow Coma Scale (GCS) and spontaneous breathing trial by ICU consultant (the investigator) till ICU discharge. Patients will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI.

Group A (Study group)

Placebo Oral Tablet DRUG

patients will receive placebo oral tablet

Group B (Control)

Eligibility Criteria

• Age: 45 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age group: Adult patients from age of 45 to70 years. (Majority of our patients falls in this age group 45-70 years, below these patients are relatively young and usually do not show delayed recovery or prolonged ventilation, while above 70 years are considered frail and more vulnerable to anesthetic medications, so we preferred to exclude them)
• Sex: Both sexes
• Elective, urgent and emergency open heart surgeries. (Most of urgent and emergency cases are either mechanical valve thrombosis or aortic dissection patients, and are more prone to prolonged mechanical ventilation and delayed recovery compared to elective patients)

You may not qualify if:

• Patients refuse to give informed consent.
• Patient younger than 45 years old, older than 70 years old.
• Off pump patients.
• Patients known hypothyroidism on levothyroxine supplementation.
• Patients known hyperthyroidism on Carbimazole.
• Those developing any form of arrhythmia L-Thyroxine will be stopped immediately and the patient will be excluded from the study.

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Faculty of Medicine ,Ain Shams University

Cairo, Egypt

Location

Related Publications (8)

• Duntas LH, Jonklaas J. Levothyroxine Dose Adjustment to Optimise Therapy Throughout a Patient's Lifetime. Adv Ther. 2019 Sep;36(Suppl 2):30-46. doi: 10.1007/s12325-019-01078-2. Epub 2019 Sep 4.

  PMID: 31485977 BACKGROUND

• Flores S, Checchia PA. Inflammatory and neurohormonal modulation for congenital heart surgery: The quest continues. J Thorac Cardiovasc Surg. 2018 Sep;156(3):1207-1208. doi: 10.1016/j.jtcvs.2018.06.004. Epub 2018 Jun 22. No abstract available.

  PMID: 30005886 BACKGROUND

• Batra YK, Singh B, Chavan S, Chari P, Dhaliwal RS, Ramprabu K. Effects of cardiopulmonary bypass on thyroid function. Ann Card Anaesth. 2000 Jul;3(2):3-6.

  PMID: 17848764 BACKGROUND

• Zhang JQ, Yang QY, Xue FS, Zhang W, Yang GZ, Liao X, Meng FM. Preoperative oral thyroid hormones to prevent euthyroid sick syndrome and attenuate myocardial ischemia-reperfusion injury after cardiac surgery with cardiopulmonary bypass in children: A randomized, double-blind, placebo-controlled trial. Medicine (Baltimore). 2018 Sep;97(36):e12100. doi: 10.1097/MD.0000000000012100.

  PMID: 30200092 BACKGROUND

• Kumar A, Taliyan R, Sharma PL. Evaluation of thyroid hormone induced pharmacological preconditioning on cardiomyocyte protection against ischemic-reperfusion injury. Indian J Pharmacol. 2012 Jan;44(1):68-72. doi: 10.4103/0253-7613.91870.

  PMID: 22345873 BACKGROUND

• Plumpton K, Haas NA. Identifying infants at risk of marked thyroid suppression post-cardiopulmonary bypass. Intensive Care Med. 2005 Apr;31(4):581-7. doi: 10.1007/s00134-004-2549-1. Epub 2005 Jan 28.

  PMID: 15678312 BACKGROUND

• Gerdes AM, Ojamaa K. Thyroid Hormone and Cardioprotection. Compr Physiol. 2016 Jun 13;6(3):1199-219. doi: 10.1002/cphy.c150012.

  PMID: 27347890 BACKGROUND

• Biondi B, Klein I. Hypothyroidism as a risk factor for cardiovascular disease. Endocrine. 2004 Jun;24(1):1-13. doi: 10.1385/ENDO:24:1:001.

  PMID: 15249698 BACKGROUND

MeSH Terms

Conditions

Delayed Emergence from Anesthesia; Euthyroid Sick Syndromes

Interventions

Thyroxine

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Thyroid Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr.Mohammed Abd Al Jawad,Professor of cardiac surgery
• Organization: Ain Shams University

mohammed_abdaljawad@med.asu.edu.eg

+201111219461

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of Anesthesia,ICU and pain management

Model Details: This study is a prospective, randomized controlled trial that will study the postoperative clinical outcomes of levothyroxine supplementation in delayed recovery or prolonged ventilation patients post cardiac surgery. Randomization will be performed using a computer-generated randomization sequence and allocation concealment to be maintained all through the time of procedure, by using opaque, numbered, and sealed envelopes. Patients will be randomly allocated by computer generated randomization into two groups A and B: * Group A (Study group): patients receiving oral supplementation of levothyroxine. * Group B (Control): patients receiving Placebo drug.

Study Record Dates

• First Submitted: October 24, 2024
• First Posted: October 28, 2024
• Study Start: November 30, 2024
• Primary Completion: June 15, 2025
• Study Completion: June 25, 2025
• Last Updated: August 17, 2025
• Results First Posted: August 17, 2025

Record last verified: 2025-08

Locations

EG (1)