Hydrocortisone Use During Peri-operation for Pituitary Adenomas

NCT ID: NCT04621565

Last Updated: 2020-11-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

436 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-01

Study Completion Date

2022-07-31

Brief Summary

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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

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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.

Conditions

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Pituitary Adenoma Adrenal Insufficiency Surgery

Keywords

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Pituitary Adenomas Peri-operation Hydrocortisone Adrenal Insufficiency

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
Participant, investigator, and outcome assessors are all prevented from having knowledge of the interventions assigned to individual participants. Care provider knows the individualized interventions.

Study Groups

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Hydrocortisone withholding group

Patients receive no hydrocortisone

Group Type EXPERIMENTAL

Normal saline

Intervention Type 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.

Hydrocortisone group

Patients receive routine hydrocortisone

Group Type ACTIVE_COMPARATOR

Hydrocortisone

Intervention Type 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.

Interventions

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Normal saline

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.

Intervention Type DRUG

Hydrocortisone

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.

Intervention Type DRUG

Other Intervention Names

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Intravenous normal saline Hydrocortisone sodium succinate (iv.) & Hydrocortisone (po.)

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Peking Union Medical College Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bing Xing, MD

Role: STUDY_CHAIR

Neurosurgery, Peking Union Medical College Hospital, Beijing, China

Wei Lian, MD

Role: STUDY_DIRECTOR

Neurosurgery, Peking Union Medical College Hospital, Beijing, China

Locations

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

Beijing, Beijing Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Bing Xing, MD

Role: CONTACT

Phone: +861069152530

Email: [email protected]

Xiaopeng Guo, MD

Role: CONTACT

Phone: +8617701220936

Email: [email protected]

Facility Contacts

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Bing Xing, MD

Role: primary

Xiaopeng Guo, MD

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 25775019 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30325449 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31978882 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36383383 (View on PubMed)

Other Identifiers

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ZS-2608

Identifier Type: -

Identifier Source: org_study_id