Pituitary AdenomaNCT04621565
Hydrocortisone Use During Peri-operation for Pituitary Adenomas
A study testing Normal saline and Hydrocortisone in people with Pituitary Adenoma and Adrenal Insufficiency, run by Peking Union Medical College Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Pituitary Adenoma, Adrenal Insufficiency, Surgery
- What is being tested?
- Normal saline and Hydrocortisone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 436 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2020to Jul 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Beijing, Beijing Municipality, 100730
Bing Xing, MD, +861069152530, xingbingemail@aliyun.com
Xiaopeng Guo, MD, +8617701220936, guoxiaopeng_pumch@163.com
About this study
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
The investigators hypothesize that withholding hydrocortisone during the peri-operation in patients with pituitary adenomas whose hypothalamus pituitary adrenal axis are intact are safe.
Read the 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.
- Conditions
- Pituitary Adenoma, Adrenal Insufficiency, Surgery
- Being tested
- Normal saline, Hydrocortisone
- Keywords
- Pituitary Adenomas, Peri-operation, Hydrocortisone, Adrenal Insufficiency
- Medical subject headings
- Pituitary Neoplasms, Adrenal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Normal salineDrug
Also called Intravenous 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.
HydrocortisoneDrug
Also called Hydrocortisone sodium succinate (iv.) & Hydrocortisone (po.)
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.
| Study group | Role | What they receive |
|---|---|---|
| Hydrocortisone withholding group | Experimental | Patients receive no hydrocortisone Receives: Drug: Normal saline |
| Hydrocortisone group | Active comparator | Patients receive routine hydrocortisone Receives: Drug: Hydrocortisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: During the first 3 postoperative days
Secondary 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.
Measured: From the 3rd postoperative day to the 3rd postoperative month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2020
- Study start1 Nov 2020
- Primary completionJul 2022 (estimated)
- Study completionJul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Pituitary AdenomaStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 436 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bing Xing, MD, Study chair, Neurosurgery, Peking Union Medical College Hospital, Beijing, ChinaWei Lian, MD, Study director, Neurosurgery, Peking Union Medical College Hospital, Beijing, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04621565
- Sponsor's protocol ID
- ZS-2608
- Status last verified
- Nov 2020
- First submitted
- 28 Oct 2020
- Last updated
- 9 Nov 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The individual participant data will be available upon reasonable requests to the study chair, Dr. Bing Xing, or the study director, Dr. Wei Lian.
Publications
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.
PubMed 25775019Sterl 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.
PubMed 30325449Lee 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.
PubMed 31978882Guo 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.
PubMed 36383383
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04621565
- Acronym / sponsor ID
- ZS-2608
- Conditions
- Pituitary Adenoma, Adrenal Insufficiency, Surgery
- Keywords
- Pituitary Adenomas, Peri-operation, Hydrocortisone, Adrenal Insufficiency
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 436 participants (estimated)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Study start
- 1 Nov 2020 (actual)
- Primary completion
- Jul 2022 (estimated)
- Study completion
- Jul 2022 (estimated)
- First posted
- 9 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Hydrocortisone withholding group | Experimental | Drug: Normal salinePatients receive no hydrocortisone |
| Hydrocortisone group | Active comparator | Drug: HydrocortisonePatients receive routine hydrocortisone |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Normal salineAlso: Intravenous normal salineNo 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. | Drug | Hydrocortisone withholding group |
| HydrocortisoneAlso: Hydrocortisone sodium succinate (iv.) & Hydrocortisone (po.)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. | Drug | Hydrocortisone group |
Primary outcome
Rate of newly-onset adrenal insufficiency
Time frame: During the first 3 postoperative days
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.
1 secondary outcome
Rate of newly-onset adrenal insufficiency
Time frame: From the 3rd postoperative day to the 3rd postoperative month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2020.
- Background: PubMed 25775019Tohti 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.
- Background: PubMed 30325449Sterl 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.
- Background: PubMed 31978882Lee 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.
- Derived from this study: PubMed 36383383Guo 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.
- Individual participant dataSharing planned: No. The individual participant data will be available upon reasonable requests to the study chair, Dr. Bing Xing, or the study director, Dr. Wei Lian.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bing Xing, MD study chair
Neurosurgery, Peking Union Medical College Hospital, Beijing, China
Wei Lian, MD study director
Neurosurgery, Peking Union Medical College Hospital, Beijing, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Normal saline and Hydrocortisone in people with Pituitary Adenoma and Adrenal Insufficiency, run by Peking Union Medical College Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Bing Xing, MD (+861069152530, xingbingemail@aliyun.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of newly-onset adrenal insufficiency (time frame: During the first 3 postoperative days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04621565, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2020.