Effect of Perioperative Glucocorticoid Replacement on Prognosis of Surgical Patients With Sellar Lesions

The purpose of this four-arm randomized controlled study is to determine whether eliminating glucocorticoids (GC) replacement in perioperative period in surgical patients with sellar lesion could result in similar or better outcomes comparing to traditional replacement therapy, regarding postoperative recovery of pituitary function and other postoperative complications (infection, pain, quality of life, recurrence). Surgical patients of our center with MRI-confirmed diagnosis of sellar lesion will be enrolled, insulin tolerance test (ITT) will be performed for assessment of the pituitary function at enrollment. Patients with normal pituitary function will be randomized into non-GC replacement group (group A) and low-dose GC replacement group (group B), while patients with impaired pituitary function will be randomized into low-dose GC replacement group (group C) and high-dose GC replacement group (group D). The primary outcome is the hypothalamic-pituitary-adrenal (HPA) -axis function of the patients, evaluated by plasma cortisol and adrenocorticotropic hormone (ACTH) levels. The secondary outcomes include the hypothalamic-pituitary-thyroid (HPT) axis function (TSH, thyroid-stimulating hormone, free T3, free T4), postoperative water-electrolyte balance, infection, recurrence and health-related quality of life.

Study Overview

• Status: Unknown
• Conditions: Pituitary Neoplasms; Craniopharyngiomas
• Intervention / Treatment: Drug: Hydrocortisone; Drug: Prednisone

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Senlin Yin, M.D.; Phone Number: +86 13072808795; Email: enforest@gmail.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital, Sichuan University
      • Contact: Senlin Yin, M.D.; Phone Number: +86 13072808795; Email: enforest@gmail.com
      • Principal Investigator: Shu Jiang, M.D.
      • Sub-Investigator: Senlin Yin, M.D.
      • Sub-Investigator: Peizhi Zhou, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age >= 18
• Surgical patients with MRI-confirmed diagnosis of sellar lesions (non-functioning pituitary adenoma or craniopharyngioma)

Exclusion Criteria:

• Patients with pre-existing hyperthyroidism or Cushing's syndrome
• Patients with long-term glucocorticoids replacement history
• Patients with other co-morbidities that pose known influence upon the HPA-axis function (cardiovascular or cerebrovascular disease, metabolic disease or epilepsy)
• Patients with severe panhypopituitarism
• Patients with history of radiotherapy of the pituitary gland

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: A. Normal function, non-GC replacement; No glucocorticoid replacement will be given perioperatively.
Active Comparator: B. Normal function, low-dose GC; Hydrocortisone 100mg i.v. before anesthesia induction, and postoperative day 1. 80mg hydrocortisone at day 2; 60mg at day 3; 20mg at day 4; 5mg oral prednisone acetate tablet at day 4 and day 5; 2.5mg at day 6;	Drug: Hydrocortisone; used intravenously; Drug: Prednisone; used as tablet form
Active Comparator: C. Impaired function, low-dose GC; Hydrocortisone 100mg i.v. before anesthesia induction, and postoperative day 1. 80mg hydrocortisone at day 2; 60mg at day 3; 20mg at day 4; 5mg oral prednisone acetate tablet at day 4 and day 5; 2.5mg at day 6;	Drug: Hydrocortisone; used intravenously; Drug: Prednisone; used as tablet form
Active Comparator: D. Impaired function, high-dose GC; Hydrocortisone 100mg i.v. before anesthesia induction, and postoperative day 1 and day 2. 60mg hydrocortisone at day 3; 60mg at day 3; 20mg at day 4; 5mg oral prednisone acetate tablet per day, since postoperative day 3.	Drug: Hydrocortisone; used intravenously; Drug: Prednisone; used as tablet form

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline plasma cortisol level	Plasma cortisol at 8:00, 16:00, 24:00 respectively	1, 3, 5, 7, 30, 90, 180, 360 days post-op
Change from baseline plasma ACTH level	ACTH at 8:00;	1, 3, 5, 7, 30, 90, 180, 360 days post-op
Change from baseline 24-hour urine free cortisol	24-hour urine free cortisol	1, 3, 5, 7, 30, 90, 180, 360 days post-op
Change from baseline insulin tolerance test result	insulin tolerance test result	7, 30, 90 days post-op

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline plasma TSH level	plasma TSH level	1, 3, 5, 7, 30, 90, 180, 360 days post-op
Sodium, potassium concentration in the blood and urine	Concentration of sodium, potassium in the blood and urine	Daily post-op,for the duration of hospital stay, an expected average of 7 days
Number of patients with postoperative infection	Routine blood test, body temperature fluctuation, cerebrospinal fluid test if necessary.	For the duration of hospital stay, an expected average of 7 days
Change from baseline health-related quality of life	The 15-Dimensions measure of health-related quality of life	7, 30, 90 days post-op
Number of patients with recurred tumor	Enhanced MRI scan of the sellar region.	3,6,12 months after surgery
Change from baseline plasma free T3 level	plasma free T3 level	1, 3, 5, 7, 30, 90, 180, 360 days post-op
Change from baseline plasma free T4 level	plasma free T4 level	1, 3, 5, 7, 30, 90, 180, 360 days post-op
Urine output	24-hour urine output	Daily post-op,for the duration of hospital stay, an expected average of 7 days

Collaborators and Investigators

• Sponsor: West China Hospital
• Investigators: Principal Investigator: Shu Jiang, M.D., West China Hospital, Sichuan University, Chengdu, Sichuan, PR China

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Anticipated): August 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: July 5, 2014
• First Submitted That Met QC Criteria: July 11, 2014
• First Posted (Estimate): July 15, 2014

Study Record Updates

• Last Update Posted (Estimate): July 15, 2014
• Last Update Submitted That Met QC Criteria: July 11, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Hydrocortisone; Replacement therapy; Pituitary adenomas
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Musculoskeletal Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Hypothalamic Diseases; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Bone Diseases; Bone Neoplasms; Pituitary Neoplasms; Pituitary Diseases; Craniopharyngioma; Adamantinoma; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone; Hydrocortisone
• Other Study ID Numbers: WestChina-2013137