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Postoperative nausea and vomiting (PONV) and pain are the most common causes of Post Anesthesia Care Unit (PACU) discharge delay, with untreated PONV occurring in 20-30% of post-surgical patients. The effect of guanfacine (GF) administration on pain and nausea scores will be assessed with two groups. One group will receive 1 mg of GF to take orally and the other group will receive a similar appearing placebo (containing no drug) to take orally.
Pain after surgery is commonly treated with narcotics which can potentiate PONV, further delaying PACU discharge. In multiple studies, alpha-2 agonists such as clonidine and dexmedetomidine reduce both the incidence of PONV and post-op pain, as well as requirements for postoperative analgesics. These actions are mediated via central alpha-2A receptors (A2AR). Of the A2AR agonists, guanfacine, though a weak antihypertensive agent, has the highest selectivity for the A2AR, but to date is untested for its potential to treat either PONV or post-operative pain.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Guanfacine | Experimental | Guanfacine 1 mg capsule by mouth, one time prior to surgery. |
|
| Placebo | Placebo Comparator | Placebo with a similar appearance to guanfacine by mouth one time prior to surgery |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Guanfacine | Drug | Patients will receive 1 mg of guanfacine to take orally. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of PONV Score of Assessments Done at 15 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | Comparison of PONV Score of assessments done at 15 minutes after arrival in PACU using the nVRS when 0 is no nausea and 10 is worst nausea | 15 minutes after arriving in PACU |
| Comparison of PONV Score of Assessments Done at 30 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | Comparison of PONV Score of assessments done at 30 minutes after arrival in PACU using the nVRS when 0 is no nausea and 10 is worst nausea | 30 minutes after arriving in PACU |
| Comparison of PONV Score of Assessments Done at 60 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | Comparison of PONV Score of assessments done at 60 minutes after arrival in PACU using the nVRS when 0 is no nausea and 10 is worst nausea | 60 minutes after arriving in PACU |
| Postoperative Nausea Assessment Using 11-point Nausea Scale (nVRS) | PONV assessed using nVRS at 24 hours postop when 0 is no nausea and 10 is worst nausea. | 24 hours post op |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | Maximum postoperative pain assessment assessed in PACU at 15, 30 and 60 minutes after PACU arrival using VAS when 0 is no pain and 10 is worst pain | 15, 30, 60 minutes after arriving in PACU |
| Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stephen T Harvey, MD | Vanderbilt University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical Center | Nashville | Tennessee | 37212 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12402719 | Background | Dolin SJ, Cashman JN, Bland JM. Effectiveness of acute postoperative pain management: I. Evidence from published data. Br J Anaesth. 2002 Sep;89(3):409-23. | |
| 2857790 | Background | Luttinger D, Ferrari R, Perrone MH, Haubrich DR. Pharmacological analysis of alpha-2 adrenergic mechanisms in nociception and ataxia. J Pharmacol Exp Ther. 1985 Mar;232(3):883-9. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Guanfacine | Guanfacine 1 mg capsule by mouth, one time prior to surgery. Guanfacine: Patients will receive 1 mg of guanfacine to take orally. |
| FG001 | Placebo | Placebo with a similar appearance to guanfacine by mouth one time prior to surgery Placebo: Patients will receive a placebo containing no drug that appears similarly to guanfacine to take orally. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Guanfacine | Guanfacine 1 mg capsule by mouth, one time prior to surgery. Guanfacine: Patients will receive 1 mg of guanfacine to take orally. |
| BG001 | Placebo | Placebo with a similar appearance to guanfacine by mouth one time prior to surgery Placebo: Patients will receive a placebo containing no drug that appears similarly to guanfacine to take orally. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Comparison of PONV Score of Assessments Done at 15 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | Comparison of PONV Score of assessments done at 15 minutes after arrival in PACU using the nVRS when 0 is no nausea and 10 is worst nausea | 15 minute nVRS datapoint was not available for 2 participants in the Placebo group | Posted | Count of Participants | Participants | 15 minutes after arriving in PACU |
|
Adverse event data was collected from consent to discharge from PACU (about 7 hours)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Guanfacine | Guanfacine 1 mg capsule by mouth, one time prior to surgery. Guanfacine: Patients will receive 1 mg of guanfacine to take orally. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Stephen Harvey, MD | Vanderbilt University Medical Center | (615) 936-3198 | stephen.harvey@vumc.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 10, 2016 | Nov 16, 2018 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D020250 | Postoperative Nausea and Vomiting |
| D010149 | Pain, Postoperative |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009325 | Nausea |
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| ID | Term |
|---|---|
| D016316 | Guanfacine |
| ID | Term |
|---|---|
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D010648 | Phenylacetates |
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| Placebo |
| Drug |
Patients will receive a placebo containing no drug that appears similarly to guanfacine to take orally. |
|
Postoperative pain assessment using VAS at 24 hours postop when 0 is no pain and 10 is worst pain |
| 24 hours postop |
| Total Narcotic Requirement in PACU | Total narcotic requirement in PACU tallied in morphine equivalents during PACU stay | Time frame between arrival and discharge in PACU, approximately 90 minutes |
| Number of Doses of PONV Treatment Administered in PACU | Time frame between arrival and discharge in PACU, approximately 90 minutes |
| PACU Length of Stay in Minutes | Time frame between arrival and discharge in PACU, approximately 90 minutes |
| 3911096 | Background | Yamadera H, Ferber G, Matejcek M, Pokorny R. Electroencephalographic and psychometric assessment of the CNS effects of single doses of guanfacine hydrochloride (Estulic) and clonidine (Catapres). Neuropsychobiology. 1985;14(2):97-107. doi: 10.1159/000118212. |
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| 7695894 | Background | Goldman-Rakic PS. Cellular basis of working memory. Neuron. 1995 Mar;14(3):477-85. doi: 10.1016/0896-6273(95)90304-6. No abstract available. |
| 21796118 | Background | Wang M, Gamo NJ, Yang Y, Jin LE, Wang XJ, Laubach M, Mazer JA, Lee D, Arnsten AF. Neuronal basis of age-related working memory decline. Nature. 2011 Jul 27;476(7359):210-3. doi: 10.1038/nature10243. |
| 3318747 | Background | Goldman-Rakic PS. Circuitry of the frontal association cortex and its relevance to dementia. Arch Gerontol Geriatr. 1987 Sep;6(3):299-309. doi: 10.1016/0167-4943(87)90029-x. |
| 7860456 | Background | Hunt RD, Arnsten AF, Asbell MD. An open trial of guanfacine in the treatment of attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 1995 Jan;34(1):50-4. doi: 10.1097/00004583-199501000-00013. |
| 22461743 | Background | Arnsten AF, Jin LE. Guanfacine for the treatment of cognitive disorders: a century of discoveries at Yale. Yale J Biol Med. 2012 Mar;85(1):45-58. Epub 2012 Mar 29. |
| 24709495 | Background | Zhao X, Tong D, Long B, Wu X. [Effects of different doses of dexmedetomidine on the recovery quality from general anesthesia undergoing thyroidectomy]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2014 Apr;26(4):239-43. doi: 10.3760/cma.j.issn.2095-4352.2014.04.008. Chinese. |
| 22546966 | Background | Blaudszun G, Lysakowski C, Elia N, Tramer MR. Effect of perioperative systemic alpha2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of randomized controlled trials. Anesthesiology. 2012 Jun;116(6):1312-22. doi: 10.1097/ALN.0b013e31825681cb. |
| 18987053 | Background | Lin TF, Yeh YC, Lin FS, Wang YP, Lin CJ, Sun WZ, Fan SZ. Effect of combining dexmedetomidine and morphine for intravenous patient-controlled analgesia. Br J Anaesth. 2009 Jan;102(1):117-22. doi: 10.1093/bja/aen320. Epub 2008 Nov 5. |
| 16803911 | Background | Gurbet A, Basagan-Mogol E, Turker G, Ugun F, Kaya FN, Ozcan B. Intraoperative infusion of dexmedetomidine reduces perioperative analgesic requirements. Can J Anaesth. 2006 Jul;53(7):646-52. doi: 10.1007/BF03021622. |
| 17023769 | Background | Ozkose Z, Demir FS, Pampal K, Yardim S. Hemodynamic and anesthetic advantages of dexmedetomidine, an alpha 2-agonist, for surgery in prone position. Tohoku J Exp Med. 2006 Oct;210(2):153-60. doi: 10.1620/tjem.210.153. |
| 18499604 | Background | Tufanogullari B, White PF, Peixoto MP, Kianpour D, Lacour T, Griffin J, Skrivanek G, Macaluso A, Shah M, Provost DA. Dexmedetomidine infusion during laparoscopic bariatric surgery: the effect on recovery outcome variables. Anesth Analg. 2008 Jun;106(6):1741-8. doi: 10.1213/ane.0b013e318172c47c. |
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| 10485781 | Background | Apfel CC, Laara E, Koivuranta M, Greim CA, Roewer N. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology. 1999 Sep;91(3):693-700. doi: 10.1097/00000542-199909000-00022. |
| 12766651 | Background | Aubrun F, Langeron O, Quesnel C, Coriat P, Riou B. Relationships between measurement of pain using visual analog score and morphine requirements during postoperative intravenous morphine titration. Anesthesiology. 2003 Jun;98(6):1415-21. doi: 10.1097/00000542-200306000-00017. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Primary | Comparison of PONV Score of Assessments Done at 30 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | Comparison of PONV Score of assessments done at 30 minutes after arrival in PACU using the nVRS when 0 is no nausea and 10 is worst nausea | Posted | Count of Participants | Participants | 30 minutes after arriving in PACU |
|
|
|
| Primary | Comparison of PONV Score of Assessments Done at 60 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | Comparison of PONV Score of assessments done at 60 minutes after arrival in PACU using the nVRS when 0 is no nausea and 10 is worst nausea | nVRS data was not available for 1 participant in the Guanfacine group | Posted | Count of Participants | Participants | 60 minutes after arriving in PACU |
|
|
|
| Primary | Postoperative Nausea Assessment Using 11-point Nausea Scale (nVRS) | PONV assessed using nVRS at 24 hours postop when 0 is no nausea and 10 is worst nausea. | Only 70 patients (32 in guanfacine arm; 38 in placebo arm) responded to follow-up phone call and provided PONV data at the 24 hour timepoint. | Posted | Median | Inter-Quartile Range | score on a scale | 24 hours post op |
|
|
|
| Secondary | Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | Maximum postoperative pain assessment assessed in PACU at 15, 30 and 60 minutes after PACU arrival using VAS when 0 is no pain and 10 is worst pain | Data unavailable for 2 participants in the placebo group at 15 minute time point, 1 participant in the placebo group at the 30 minute time point, | Posted | Count of Participants | Participants | 15, 30, 60 minutes after arriving in PACU |
|
|
|
| Secondary | Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | Postoperative pain assessment using VAS at 24 hours postop when 0 is no pain and 10 is worst pain | Based on only 71 participants to post operative questionnaire. | Posted | Median | Inter-Quartile Range | score on a scale | 24 hours postop |
|
|
|
| Secondary | Total Narcotic Requirement in PACU | Total narcotic requirement in PACU tallied in morphine equivalents during PACU stay | Data was not available for 1 participant in the placebo group. | Posted | Median | Inter-Quartile Range | morphine equivalents | Time frame between arrival and discharge in PACU, approximately 90 minutes |
|
|
|
| Secondary | Number of Doses of PONV Treatment Administered in PACU | Data missing for1 participants in the placebo group and 1 participant in the Guanfacine group. | Posted | Count of Participants | Participants | Time frame between arrival and discharge in PACU, approximately 90 minutes |
|
|
|
| Secondary | PACU Length of Stay in Minutes | Posted | Median | Inter-Quartile Range | minutes | Time frame between arrival and discharge in PACU, approximately 90 minutes |
|
|
|
| 0 |
| 40 |
| 0 |
| 40 |
| 0 |
| 40 |
| EG001 | Placebo | Placebo with a similar appearance to guanfacine by mouth one time prior to surgery Placebo: Patients will receive a placebo containing no drug that appears similarly to guanfacine to take orally. | 0 | 44 | 0 | 44 | 0 | 44 |
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| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D014839 | Vomiting |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D000146 |
| Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| Moderate/Severe (nVRS 6-10) |
|
| Moderate/Severe (nVRS 6-10) |
|
| Mild (Pain nVRS 1-5) |
|
| Moderate/Severe (Pain nVRS 6-10) |
|
| 30 minutes after PACU admission |
|
|
| 60 minutes after PACU admission |
|
|
| Two doses |
|