Efficacy of Thyroid Hormone Replacement for Secondary Hypothyroidism Following Intracerebral Hemorrhage

NCT06353555 | Recruiting

• 1 other identifier: PUMCH-20240311
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Low levels of serum triiodothyronine (T3) thyroid hormones (T4) are a strong predictor of mortality and poor prognosis in critical care patients. Few reports, however, have focused on neurocritical patients. Patients with severe neurological diseases often experience more complications and exhibit higher mortality rates, and many studies have provided evidence for a low T3/T4 state being an important prognostic indicator in such cases; Lieberman et al. found that 87% of individuals with severe traumatic brain injury have thyroid function below the mid-normal range. Other researchers showed that low T3 syndrome is a predictor of poor prognosis in cerebral infarction patients; their findings indicated the central hypothyroidism and disturbance of thyroid hormone metabolism were involved. Low T3 syndrome is common in patients with brain tumors and has been shown to be associated with shorter survival in glioma patients. Despite these observations, however, whether the thyroid hormone abnormalities in the critically ill are a physiological adaptation or a pathological change, and whether hormone replacement therapy (HRT) can benefit such patients, remain to be established. As acute progression ceases, thyroid hormone levels may return to normal. This may imply that thyroid hormone supplements could improve the prognosis of patients with secondary hypothyroidism. Previous clinical studies have examined the effect of thyroid HRT on patients undergoing cardiac surgery; patients with malnutrition, heart failure, or acute renal failure; and premature infants with acute respiratory distress syndrome. Most of these past studies found no significant positive effects on prognosis, and no harmful effects either. Some smaller studies have demonstrated potential promise for the use of HRT; for example, one study showed that T3 supplementation in patients undergoing cardiac surgery could lead to less need for inotropic support and better hemodynamic parameters. There are no reports of thyroid HRT improving the prognosis of neurocritical patients with secondary hypothyroidism. The application of hormone replacement therapy in the treatment of neurocritical patients with secondary hypothyroidism remains controversial. This study aims to explore the safety and effectiveness of thyroid hormone replacement therapy in patients with spontaneous intracerebral hemorrhage and concomitant secondary hypothyroidism.

Conditions

Intracerebral Hemorrhage; Low T3 Syndrome; Neurocritical Care; Hormone Replacement Therapy

Outcome Measures

Primary Outcomes (4)

• blood pressure

  Systolic blood pressure in mmHg, diastolic blood pressure in mmHg, mean arterial pressure in mmHg, heart rate in beat per minute

  Day1、2、3、5、7（ 9:00 17:00 21:00）

• cerebral blood flow dynamics

  Cerebral blood volume in ml/100g; cerebral blood flow in ml/(100g·min)

  Day 7

• Whether to use vasoactive vasopressors

  Blood pressure in mmHg before and after using vasoactive vasopressors

  Day 1 to 7

• neurological function

  modified Ranking Scale score (0 to 6 score, from better to worse)

  in 90 days

Secondary Outcomes (2)

• Days of the patients received intensive care

  From date of randomization until the date of first documented progression or date of discharge from any cause, whichever came first, assessed up to 12 months

• Mechanical ventilation time

  From date of randomization until the date of first documented progression or date of discharge from any cause, whichever came first, assessed up to 12 months

Study Arms (2)

Thyroid hormone replacement therapy

EXPERIMENTAL

Upon discovering low T3 or low T4 levels, administer oral levothyroxine sodium tablets daily. If accompanied by a decrease in TSH, the regimen is 100μg qd (for individuals weighing \<75kg) or 150μg qd (for individuals weighing \>75kg). If not accompanied by a decrease in TSH, the regimen is 50μg qd. However, if thyroid function does not significantly improve within 3 days of medication, the regimen is adjusted to 100μg qd. Treatment should continue until transfer out of the NICU or discharge, with a minimum duration of 7 days.

Drug: Euthyrox

Non-thyroid hormone replacement therapy

SHAM COMPARATOR

Patients will not receive the oral levothyroxine sodium tablets.

Drug: Euthyrox

Interventions

Euthyrox DRUG

Upon discovering low T3 or low T4 levels, administer oral levothyroxine sodium tablets daily. If accompanied by a decrease in TSH, the regimen is 100μg qd (for individuals weighing \<75kg) or 150μg qd (for individuals weighing \>75kg). If not accompanied by a decrease in TSH, the regimen is 50μg qd. However, if thyroid function does not significantly improve within 3 days of medication, the regimen is adjusted to 100μg qd. Treatment should continue until transfer out of the NICU or discharge, with a minimum duration of 7 days.

Thyroid hormone replacement therapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Admittance of neurocritical patients to the Neurological Intensive Care Unit (NICU) with a Glasgow Coma Scale (GCS) score of 3-8 and supratentorial hematoma volume \>30 ml. The disease is limited to spontaneous intracerebral hemorrhage (supratentorial brain parenchyma, with or without hematoma rupture into the ventricle).
• Age: 18-80 years old.
• Onset within 24 hours.
• Free T3 \< 1.80 pg/ml or free T4 \< 0.81 ng/dl within 7 days of onset, with or without TSH \< 0.38 μIU/ml. (Specifically according to the critical values of different center laboratories' abnormal ranges).
• Emergency head CT scan completed within 24 hours of onset.

You may not qualify if:

• Organic thyroid lesions (subacute thyroiditis, chronic thyroiditis, post-thyroidectomy, thyroid radiation, hyperthyroidism), history of thyroid hormone oral replacement therapy within the past month.
• Sella region lesions.
• Baseline CT indicates irreversible brain herniation, expected survival period \<30 days.
• Severe systemic multiple injuries outside the nervous system.
• Pregnant women.
• Acute or chronic heart failure, arrhythmias, myocardial disease.
• Only TSH levels decrease while free T3 and free T4 levels remain normal.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking union medical college hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

MeSH Terms

Conditions

Cerebral Hemorrhage; Euthyroid Sick Syndromes

Interventions

Thyroxine

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; 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

Central Study Contacts

Junji Wei

CONTACT

15801056698; weijunji@pumch.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: clinical professor

Study Record Dates

• First Submitted: March 11, 2024
• First Posted: April 9, 2024
• Study Start: October 11, 2023
• Primary Completion: June 1, 2025
• Study Completion: December 31, 2025
• Last Updated: April 9, 2024

Record last verified: 2024-04

Locations

CN (1)