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Preoperative Oral Dexamethasone to Improve Recovery After Surgery

Phase 2
Conditions
Breast Cancer
Interventions
Registration Number
NCT02234466
Lead Sponsor
University of Manitoba
Brief Summary

Randomized controlled trial of pre-operative oral dexamethasone vs placebo for the improvement of quality of recovery from surgery. The study population is limited to breast surgery patients. The investigators will also look at the effect of our intervention on post operative nausea and vomiting.

Patients will be recruited before the date of their surgery and will complete the Quality of Recovery-40 (QOR-40) questionnaire before their surgery and at 24 hours post op. They will also complete a Clinically significant nausea and vomiting score upon discharge from the post anesthesia recovery room, repeated at 24 hours post op.

Detailed Description

Design: This will be a single centre randomized, double blind, parallel-group, intention to treat, controlled trial. Patients are randomly assigned to pre-operative oral dexamethasone or placebo

Group 1: Pre-operative oral dexamethasone (10mg-2 hours pre-induction) Group 2: Placebo Sample Size: 80 patients (80% power to detect a difference of 10 points in our primary endpoint)

Study duration: 8 months

Primary endpoint: Quality of recovery at 24 hours post operation, as measured on the QoR-40 Secondary endpoints: Clinically significant nausea and vomiting on discharge from Post-Anesthesia Recovery Room (PARR) and at 24 hours.

Study hypotheses:Pre-operative oral dexamethasone will improve patient quality of recovery compared to placebo.

Secondary hypothesis: Pre-operative dexamethasone will decrease clinically significant post operative nausea and vomiting in the post anesthesia recovery room and this benefit will endure at 24 hours.

Importance: Small studies in other adult populations suggest that IV dexamethasone may improve quality of recovery. IV dexamethasone is widely used off label for postoperative nausea and vomiting (PONV) prophylaxis, oral dexamethasone has not been studied for this indication but based on the pharmacodynamics of dexamethasone, and that modulation of nucleolar transcription is likely important in dexamethasone's clinical effect; an earlier administration time is likely of benefit, this could be facilitated by an oral (vs IV) route of administration. This study will provide the preliminary support (or absence of support) for a routine, inexpensive intervention to optimize patient outcome.

Background: Single, low dose perioperative dexamethasone is safe and beneficial but common timing of administration does not maximize effectiveness. IV dexamethasone improves quality of recovery in patients undergoing laparoscopic cholecystectomy and provides a potential 1.5 mm improvement in VAS pain scores in the first 6 hours post mastectomy, which is of questionable clinical significance. A study to determine if dexamethasone improves the quality of recovery in patients undergoing breast surgery is needed in order to provide evidence for change of practices and pre-operative oral dexamethasone offers the potential for routine, low cost administration without uncomfortable side effects.

Methods: Patients will be recruited pre-operatively and contacted by telephone for preliminary consent. They will receive consent documents on the morning of surgery and be randomized at that time, they will complete a pre-operative QOR-40 and receive oral dexamethasone or placebo. During their general anaesthesia (GA) they will all receive IV Ondansetron and have their blood glucose measured 2 hours after skin incision. On discharge from PARR they will have a clinically significant nausea and vomiting scale score recorded, repeated at 24 hours post op. They will also complete the QOR-40 at 24 hours post op.

Analysis: Data will be analyzed using analysis of variance, mixed models and t-tests.

Potential Pitfalls: As the QOR-40 instrument is a survey, it is prone to inter and intra patient variability. The investigators are controlling for inter-patient variability by having patients complete the instrument before surgery to collect an individual baseline. The investigators are relying on a 25% recruitment rate of eligible patients in order to complete the study in the stated timeframe. The study has an important but narrow focus, it is not feasible to perform subgroup analysis on the small study size.

Recruitment & Eligibility

Status
UNKNOWN
Sex
Female
Target Recruitment
80
Inclusion Criteria
  • Adults (18 to 80 years of age) undergoing general anesthesia for elective breast surgery (lumpectomy or mastectomy) and providing informed consent.
  • American Society of Anesthesia (ASA) class I, II, & III patients
Exclusion Criteria
  • ASA class IV and V patients
  • Pregnancy
  • Diabetes
  • History of allergy to any study medications
  • Use of steroids or anti emetics within 1 month of surgery
  • Chronic pain requiring opioid treatment
  • History of alcohol or drug abuse (including smoking tobacco)
  • Severe renal impairment (i.e. serum creatinine more than 160 umol/L)
  • Poor English comprehension or psychiatric/central nervous system disturbance that would preclude completion of the QoR-40 questionnaire

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Oral DexamethasoneOral dexamethasoneOral dexamethasone- two 4mg tabs and one 2mg tab contained within a gelatin capsule Administered a single time, 2 hours pre-induction Ondansetron 6mg IV will be administered at skin closure
Oral DexamethasoneOndansetronOral dexamethasone- two 4mg tabs and one 2mg tab contained within a gelatin capsule Administered a single time, 2 hours pre-induction Ondansetron 6mg IV will be administered at skin closure
Oral DexamethasoneGelatin capsuleOral dexamethasone- two 4mg tabs and one 2mg tab contained within a gelatin capsule Administered a single time, 2 hours pre-induction Ondansetron 6mg IV will be administered at skin closure
Gelatin pillGelatin capsuleGelatin capsule contained within second gelatin capsule. Administered a single time, 2 hours pre-induction Ondansetron 6mg IV will be administered at skin closure
Gelatin pillOndansetronGelatin capsule contained within second gelatin capsule. Administered a single time, 2 hours pre-induction Ondansetron 6mg IV will be administered at skin closure
Primary Outcome Measures
NameTimeMethod
Change from baseline in Quality of recovery at Post operative day 1 (POD1)24 hours

Quality of recovery as assessed by the QOR-40 will be assessed at POD1, with a baseline measure having been collected immediately pre-operatively.

Secondary Outcome Measures
NameTimeMethod
Post operative Nausea and Vomiting immediately post operativelyAt discharge from Post Anesthesia Recovery Room, usually within 90 mins to 180 mins after surgery

Assayed by the Clinically Significant Nausea and Vomiting Scale

Post operative Nausea and Vomiting in first 24 hoursThe first 24 hours after surgery

Post operative Nausea and Vomiting as assessed by the Clinically Significant Nausea and Vomiting scale on POD1, assessing the period from surgery until the assessment (not excluding post anesthesia recovery room)

Trial Locations

Locations (1)

Health Science Centre

🇨🇦

Winnipeg, Manitoba, Canada

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