Clinical trial NCT04621565: Hydrocortisone Use During Peri-operation for Pituitary Adenomas
Official title: Withholding Hydrocortisone vs Routine Use of Hydrocortisone During Peri-operation in Pituitary Adenoma Patients With Intact Hypothalamus-Pituitary-Adrenal Axis: Randomized Controlled Trial to Assess Safety and Complications
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pituitary Adenoma
Adrenal Insufficiency
Surgery
Keywords: Pituitary Adenomas
Peri-operation
Hydrocortisone
Adrenal Insufficiency
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2020-11-09
Enrollment: 436
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants are assigned to one of two groups, whether using hydrocortisone or not during peri-operation, in parallel for the duration of the study.
Primary purpose: PREVENTION

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.

Detailed description: Pituitary is the headquarters of the endocrine system of the body, secreting several hormones maintaining the normal function of the endocrine organs. After surgery, pituitary dysfunction is seen in a small proportion of patients, even in some patients resulting in severe consequence, i.e. adrenal insufficiency or pituitary crisis. Therefore, patients undergoing pituitary surgery have been usually given "stress dose" steroids whether their hypothalamus pituitary adrenal (HPA) axis are deficient or preserved.

Results of several retrospective studies showed that there was no significantly increase in postoperative adrenal insufficiency in no supplementation (of hydrocortisone) group than in supplementation group. Given the considerable side effects of using steroids, whether hydrocortisone administration is necessary for all patients with pituitary adenomas during peri-operation needs to be discussed.

For Chinese patients with pituitary adenomas except for those of Cushing's disease, hydrocortisone administration during the peri-operation is a routine practice. Peking Union Medical College Hospital is the China Pituitary Disease Registry Center. Here, the investigators aim to launch a single-center prospective randomized controlled trial to verify the hypothesis that withholding hydrocortisone during the peri-operation in patients with pituitary adenomas whose HPA axis are intact are safe.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Rate of newly-onset adrenal insufficiency
timeFrame: During the first 3 postoperative days
Secondary outcomes:
measure: Rate of newly-onset adrenal insufficiency
timeFrame: From the 3rd postoperative day to the 3rd postoperative month
Other outcomes:
measure: Rate of newly-developed diabetes mellitus
timeFrame: During the first 3 postoperative months
measure: Rate of newly-developed diabetes insipidus
timeFrame: During the first 3 postoperative months
measure: Concentration of blood electrolytes
timeFrame: At the 3rd postoperative month
measure: Concentration of blood cells
timeFrame: At the 3rd postoperative month
measure: Percentage of blood cells
timeFrame: At the 3rd postoperative month
measure: Concentration of indexes of coagulation function #1
timeFrame: At the 3rd postoperative month
measure: Level of international normalized ratio
timeFrame: At the 3rd postoperative month
measure: Level of D-Dimer
timeFrame: At the 3rd postoperative month
measure: Rate of deep venous thrombosis
timeFrame: During the first 3 postoperative months
measure: Rate of other complications
timeFrame: During the first 3 postoperative months
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
state: Beijing
Study officials:
affiliation: Neurosurgery, Peking Union Medical College Hospital, Beijing, China
name: Bing Xing, MD
role: STUDY_CHAIR
affiliation: Neurosurgery, Peking Union Medical College Hospital, Beijing, China
name: Wei Lian, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.