Levothyroxine Treatment for Subclinical Hypothyroidism After Head and Neck Surgery

NCT02548715 | Withdrawn Phase 2

• 1 other identifier: Pro00043413
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Patients that require treatment for cancers of the head and neck often require a combination of surgery and/or radiation and chemotherapy. Hypothyroidism is one of the most common complications, and has been associated with post-operative complications such as wound healing problems, fistula formation, and decreased quality of life and survival. Several studies have examined hypothyroidism after radiation to the head and neck, but few have examined this after non-thyroid head and neck surgery. Head and neck resection is theorized to devascularize the thyroid, thus resulting in post-operative hypothyroidism. Synthroid is a synthetic thyroid hormone often used in cases of patients with proven hypothyroidism and after surgical thyroid removal. It's use has been in effect and studied for over fifty years. Treatment algorithms for hypothyroidism are well published. However, treatment of subclinical hypothyroidism (elevated TSH with normal or near-normal T3/T4) is controversial. The rate of subclinical hypothyroidism after non-thyroid head and neck surgery is high (up to 20%), and is associated with post-operative complications as noted above. Therefore the investigators propose a double blinded randomized controlled trial comparing outcomes of patients that develop subclinical hypothyroidism after head and neck surgery, who are given a standardized dose of synthroid treatment versus those treated with placebo. The main outcomes to be examined are post-operative complications (wound healing issues, fistula formation), survival, and quality of life measures.

Conditions

Hypothyroidism; Neoplasms; Postoperative Complications

Keywords

thyroxine; Otolaryngology

Outcome Measures

Primary Outcomes (1)

• Number of patients with a post-operative wound complication

  * Rate of fistula formation * Rate of wound breakdown * Rate of post-operative infection * Rate of flap failure (dehiscence and/or necrosis requiring salvage)

  12 weeks post-operatively

Secondary Outcomes (4)

• Number of surviving patients at 6 months

  6 months post-operatively

• Number of patients with G-tube

  12 weeks post-operatively

• Quality of life based on EQ-5D7

  12 weeks post-operatively

• Number of patients with clinical depression

  12 weeks post-operatively

Study Arms (2)

Control

PLACEBO COMPARATOR

Daily placebo

Drug: Placebo

Treatment

EXPERIMENTAL

Participants administered daily levothyroxine at 1.6mcg/kg to a target normal TSH, measured at 6 weeks after the initiation of therapy

Drug: Levothyroxine

Interventions

Levothyroxine DRUG

Also known as: Synthroid

Treatment

Placebo DRUG

Control

Eligibility Criteria

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

You may qualify if:

• Biopsy proven head and neck cancer, as defined by AJCC staging system
• Treated with surgery in Edmonton, Alberta
• Treated with curative intent
• Diagnosis of sub-clinical hypothyroidism after head and neck surgery (TSH 4-10mIU/L, and free T4 10-24pmol/L)

You may not qualify if:

• Head and neck cancer of the thyroid gland, or other subsite involving the thyroid gland
• Underwent previous treatment for a different head and neck cancer
• History of radiation therapy and or chemotherapy to the head and neck
• History of thyroid disease as follows:
• Hypothyroidism
• Hyperthyroidism
• Autoimmune thyroid disease including Grave's disease and Hashimoto's thyroiditis
• History of thyroiditis
• History of diabetes mellitus
• History of long term steroid usage
• History of immunocompromise
• History of thyroid surgery
• History of ischemic heart disease
• Age \>80
• Patients taking a medication that may alter the metabolism or interact with levothyroxine, which they cannot safely stop (see Appendix A).

Sponsors & Collaborators

• University of Alberta: lead

MeSH Terms

Conditions

Hypothyroidism; Neoplasms; Postoperative Complications

Interventions

Thyroxine

Condition Hierarchy (Ancestors)

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

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2015
• First Posted: September 14, 2015
• Study Start: July 1, 2015
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: July 13, 2022

Record last verified: 2022-07