Hydrocortisone Use During Peri-operation for Pituitary Adenomas

NCT04621565 | Unknown

• 1 other identifier: ZS-2608
• Study Type: interventional
• Target: 436
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesize that withholding hydrocortisone during the peri-operation in patients with pituitary adenomas whose hypothalamus pituitary adrenal axis are intact are safe.

Conditions

Pituitary Adenoma; Adrenal Insufficiency; Surgery

Keywords

Pituitary Adenomas; Peri-operation; Hydrocortisone; Adrenal Insufficiency

Outcome Measures

Primary Outcomes (1)

• Rate of newly-onset adrenal insufficiency

  Adrenal insufficiency: lower-than-normal serum cortisol level at 8 a.m., plus the following related symptoms, including serious fatigue, muscle weakness, decreased appetite, nausea, vomiting, diarrhea, low blood pressure, palpitation, and fever.

  During the first 3 postoperative days

Secondary Outcomes (1)

• Rate of newly-onset adrenal insufficiency

  From the 3rd postoperative day to the 3rd postoperative month

Other Outcomes (10)

• Rate of newly-developed diabetes mellitus

  During the first 3 postoperative months

• Rate of newly-developed diabetes insipidus

  During the first 3 postoperative months

• Concentration of blood electrolytes

  At the 3rd postoperative month

Study Arms (2)

Hydrocortisone withholding group

EXPERIMENTAL

Patients receive no hydrocortisone

Drug: Normal saline

Hydrocortisone group

ACTIVE COMPARATOR

Patients receive routine hydrocortisone

Drug: Hydrocortisone

Interventions

Normal saline DRUG

No hydrocortisone or other steroids are given before, during, and after the surgery, except that patients develop postoperative adrenal insufficiency. If a patient develops postoperative adrenal insufficiency, he/she needs to receive hydrocortisone treatment (20mg at 0800 and 20mg at 1600) for one month and then check the level of morning serum cortisol to decide if it is time to start the hydrocortisone taper program.

Also known as: Intravenous normal saline

Hydrocortisone withholding group

Hydrocortisone DRUG

Hydrocortisone sodium succinate is given on the operation day (100mg at 0800 \& 100mg at 2000), the postoperative day 1 (100mg at 0800 \& 50mg at 2000), and the postoperative day 2 (25mg at 0800). Hydrocortisone (po.) is then given starting from the afternoon of postoperative day 2 (20mg at 1600 and 0800) to the end of the first postoperative week, and 20mg at 0800 during the second postoperative week. This is called the "hydrocortisone taper program". If a patient develops postoperative adrenal insufficiency, he/she needs to receive hydrocortisone treatment (20mg at 0800 and 20mg at 1600) for one month and then check the level of morning serum cortisol to decide if it is time to start the hydrocortisone taper program.

Also known as: Hydrocortisone sodium succinate (iv.) & Hydrocortisone (po.)

Hydrocortisone group

Eligibility Criteria

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

You may qualify if:

• Patients with pituitary adenomas that need surgical resection of the tumor, whose hypothalamus-pituitary-adrenal axis are intact
• Patients of either gender aged from 18 years to 70 years

You may not qualify if:

• Patients with Cushing's disease
• Patients with pituitary adenomas who have already developed secondary adrenal insufficiency before surgery
• Patients with pituitary apoplexy or other acute pituitary conditions that need emergency surgery
• The postoperative pathology result indicates that the tumor is not a pituitary adenoma
• Patients that refuse to participate in the study or those who ask to quit after enrollment

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, Beijing Municipality, 100730, China

RECRUITING

Related Publications (4)

• Tohti M, Li J, Zhou Y, Hu Y, Yu Z, Ma C. Is peri-operative steroid replacement therapy necessary for the pituitary adenomas treated with surgery? A systematic review and meta analysis. PLoS One. 2015 Mar 16;10(3):e0119621. doi: 10.1371/journal.pone.0119621. eCollection 2015.

  PMID: 25775019 BACKGROUND

• Sterl K, Thompson B, Goss CW, Dacey RG, Rich KM, Zipfel GJ, Chicoine MR, Kim AH, Silverstein JM. Withholding Perioperative Steroids in Patients Undergoing Transsphenoidal Resection for Pituitary Disease: Randomized Prospective Clinical Trial to Assess Safety. Neurosurgery. 2019 Aug 1;85(2):E226-E232. doi: 10.1093/neuros/nyy479.

  PMID: 30325449 BACKGROUND

• Lee HC, Yoon HK, Kim JH, Kim YH, Park HP. Comparison of intraoperative cortisol levels after preoperative hydrocortisone administration versus placebo in patients without adrenal insufficiency undergoing endoscopic transsphenoidal removal of nonfunctioning pituitary adenomas: a double-blind randomized trial. J Neurosurg. 2020 Jan 24;134(2):526-534. doi: 10.3171/2019.11.JNS192381. Print 2021 Feb 1.

  PMID: 31978882 BACKGROUND

• Guo X, Zhang D, Pang H, Wang Z, Gao L, Wang Y, Ma W, Lian W, Xing B; ZS-2608 Trial Team. Safety of Withholding Perioperative Hydrocortisone for Patients With Pituitary Adenomas With an Intact Hypothalamus-Pituitary-Adrenal Axis: A Randomized Clinical Trial. JAMA Netw Open. 2022 Nov 1;5(11):e2242221. doi: 10.1001/jamanetworkopen.2022.42221.

  PMID: 36383383 DERIVED

MeSH Terms

Conditions

Pituitary Neoplasms; Adrenal Insufficiency

Interventions

Saline Solution; Hydrocortisone

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypothalamic Diseases; Pituitary Diseases; Endocrine System Diseases; Adrenal Gland Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Bing Xing, MD

  Neurosurgery, Peking Union Medical College Hospital, Beijing, China

  STUDY CHAIR

• Wei Lian, MD

  Neurosurgery, Peking Union Medical College Hospital, Beijing, China

  STUDY DIRECTOR

Central Study Contacts

Bing Xing, MD

CONTACT

+861069152530; xingbingemail@aliyun.com

Xiaopeng Guo, MD

CONTACT

+8617701220936; guoxiaopeng_pumch@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participant, investigator, and outcome assessors are all prevented from having knowledge of the interventions assigned to individual participants. Care provider knows the individualized interventions.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are assigned to one of two groups, whether using hydrocortisone or not during peri-operation, in parallel for the duration of the study.

Study Record Dates

• First Submitted: October 28, 2020
• First Posted: November 9, 2020
• Study Start: November 1, 2020
• Primary Completion: July 1, 2022
• Study Completion: July 1, 2022
• Last Updated: November 9, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)