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We hypothesize that the effects of non-steroidal anti-inflammatory drugs (NSAIDS) for pain relief among patients with pituitary adenomas undergoing transnasal transsphenoidal surgeries are non-inferior to tramadol. We aim to launch a single-center randomized clinical trial to verify this hypothesis.
Postoperative pain is an important clinical concern and quality-of-care metric, yet it is undertreated in neurosurgical patients. Approximately 40% of inpatients complain of severe pain postoperatively, and only 56% of these patients indicate that their pain is well controlled. In addition, pain is a common cause of delayed discharge and unplanned hospital readmission.
Pituitary adenoma is the second most common benign primary central nervous system tumor, and transnasal transsphenoidal (TTS) has long taken over craniotomy to be the first-line surgical approach for pituitary tumor resection. TTS significantly reduces patient's surgical trauma, shortens the operation time, reduces surgery-related complications, and increases total tumor resection rate compared with the previously used craniotomy. However, given that the nasal mucosa is extremely sensitive, the feeling of pain is more obvious after surgery via TTS approach than via craniotomy.
Opioids such as morphine and pethidine are the most effective post-surgical analgesics, but they have a series of side effects, such as drug addiction, decreased gastrointestinal motility, nausea and vomiting. Opioids are not an analgesic that must be used after TTS surgery. NSAIDS, such as parecoxib and lexone, and tramadol are also commonly used analgesics after surgery, and they are also effective. NSAIDS is a first-tier painkiller, and tramadol is a second-tier drug. There is no evidence-based evidence recommending the preferred choice of these two drugs. Which of NSAIDS and tramadol has the better analgesic effect and which drug brings lower side effects to patients is still unclear. The clinical application of the two drugs is entirely based on the personal habits of the surgeon.
Therefore, we plan to conduct a prospective randomized controlled trial to explore: whether the analgesic effect of NSAIDS is non-inferior than tramadol; and whether the side effects of NSAIDS are not higher than tramadol. This result will guide us in clinical pain management for patients with pituitary adenomas after surgery via TTS approach.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NSAIDs | Experimental | Parecoxib (iv.) for once & Loxoprofen (po.) for routine use during the first 3 postop. days. |
|
| Tramadol | Active Comparator | Tramadol (im.) for once & Tramcontin (po.) for routine use during the first 3 postop. days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NSAID | Drug | Immediately after the operation, the patient is given (parecoxib 40 mg + sodium chloride 100 ml) intravenously once, and then given (loxoprofen 60 mg) orally twice a day during the first three postoperative days. |
| Measure | Description | Time Frame |
|---|---|---|
| The VAS scores of patients | visual analogue scale score that represents the patient's subjective pain perception | 24 hours after the surgery |
| Measure | Description | Time Frame |
|---|---|---|
| The VAS scores of patients | visual analogue scale score that represents the patient's subjective pain perception | 48 hours after the surgery |
| The VAS scores of patients | visual analogue scale score that represents the patient's subjective pain perception |
| Measure | Description | Time Frame |
|---|---|---|
| The side effects of the drugs | Including but not limited to nausea, vomiting, upset stomach, stomach pain, gastrorrhagia, dizziness and skin rash, while using these drugs | during the first 3 postoperative days |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Bing Xing, MD | Contact | +861069152530 | xingbingemail@aliyun.com | |
| Xiaopeng Guo, MD | Contact | +8617701220936 | guoxiaopeng_pumch@163.com |
| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College | Recruiting | Beijing | Beijing Municipality | 100730 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26967774 | Background | Titsworth WL, Abram J, Guin P, Herman MA, West J, Davis NW, Bushwitz J, Hurley RW, Seubert CN. A prospective time-series quality improvement trial of a standardized analgesia protocol to reduce postoperative pain among neurosurgery patients. J Neurosurg. 2016 Dec;125(6):1523-1532. doi: 10.3171/2015.10.JNS15698. Epub 2016 Mar 11. | |
| 8799542 |
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The individual participant data can be made available upon reasonable request to the study chair, Dr. Bing Xing, or the study director, Dr. Wei Lian.
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Aug 29, 2021 | |
| Reset | Sep 23, 2021 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Aug 29, 2021 | Sep 23, 2021 |
| ID | Term |
|---|---|
| D010911 | Pituitary Neoplasms |
| D010146 | Pain |
| D000377 | Agnosia |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D007029 | Hypothalamic Neoplasms |
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| ID | Term |
|---|---|
| D000894 | Anti-Inflammatory Agents, Non-Steroidal |
| C409945 | parecoxib |
| C040656 | loxoprofen |
| D014147 | Tramadol |
| ID | Term |
|---|---|
| D018712 | Analgesics, Non-Narcotic |
| D000700 | Analgesics |
| D018689 | Sensory System Agents |
| D018373 | Peripheral Nervous System Agents |
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Participants are assigned to one of two groups in parallel during the study, using the method of randomization. The ratio is 1:1.
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The participant, investigator and outcome assessors are all prevented from having knowledge of the interventions assigned to individual participants. Only the care provider knows individual specified intervention.
|
| Tramadol | Drug | Immediately after the operation, the patient is given (tramadol 100 mg) intramuscularly once, and then given (tramcontin 100 mg) orally twice a day during the first three postoperative days. |
|
|
| 72 hours after the surgery |
| The dynamic trend of VAS scores of patients during the first 3 postoperative days | visual analogue scale score that represents the patient's subjective pain perception | during the first 3 postoperative days |
| Quiney N, Cooper R, Stoneham M, Walters F. Pain after craniotomy. A time for reappraisal? Br J Neurosurg. 1996 Jun;10(3):295-9. doi: 10.1080/02688699650040179. |
| 15763409 | Background | Joshi GP, Ogunnaike BO. Consequences of inadequate postoperative pain relief and chronic persistent postoperative pain. Anesthesiol Clin North Am. 2005 Mar;23(1):21-36. doi: 10.1016/j.atc.2004.11.013. |
| 28298041 | Background | Shepherd DM, Jahnke H, White WL, Little AS. Randomized, double-blinded, placebo-controlled trial comparing two multimodal opioid-minimizing pain management regimens following transsphenoidal surgery. J Neurosurg. 2018 Feb;128(2):444-451. doi: 10.3171/2016.10.JNS161355. Epub 2017 Mar 3. |
| 28170483 | Background | Molitch ME. Diagnosis and Treatment of Pituitary Adenomas: A Review. JAMA. 2017 Feb 7;317(5):516-524. doi: 10.1001/jama.2016.19699. |
| D015173 |
| Supratentorial Neoplasms |
| D001932 | Brain Neoplasms |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D007027 | Hypothalamic Diseases |
| D010900 | Pituitary Diseases |
| D004700 | Endocrine System Diseases |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010468 | Perceptual Disorders |
| D019954 | Neurobehavioral Manifestations |
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D000893 | Anti-Inflammatory Agents |
| D045506 | Therapeutic Uses |
| D018501 | Antirheumatic Agents |
| D003511 | Cyclohexanols |
| D000441 | Hexanols |
| D005233 | Fatty Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D004123 | Dimethylamines |
| D008744 | Methylamines |
| D000588 | Amines |
| D008055 | Lipids |