Effect of Celecoxib on Postoperative Analgesia and Disease Severity in AERD Patients With CRS

1. Background: Chronic rhinosinusitis (CRS) affects up to 5% of Canadians and isassociated with significant morbidity. It is characterized by inflammation of themucosa of the nose and paranasal sinuses of at least 12 consecutive weeks' duration.Patients suffering from CRS are bothered on a daily basis by nasal obstruction,nasal discharge, facial pain, and an impaired sense of smell among other symptoms.Although not typically a life‐threatening condition, CRS can drastically reduce apatient's quality of life as well as their workplace productivity. In fact, this hasbeen demonstrated in the literature, with one study estimating the annualproductivity cost of refractory CRS at about $10,000 per patient.Fortunately, effective management strategies are available. Mild to moderate diseasecan often be managed safely with long term use of topical glucocorticoids and nasalsaline lavage. For more severe CRS unresponsive to appropriate medical therapy, oralglucocorticoids can be effective in the short term, but surgical treatment can helpachieve long‐term control of symptoms when initial medical therapy has failed. Thisis typically done via endoscopic sinus surgery (ESS), and its goal is tore‐establish physiological patterns of ventilation and mucociliary clearance inpatients with CRS, as well as establish access for topical therapy delivery. ESS isconsidered the gold standard of management for CRS and has proven to be highlyeffective in reducing the burden of inflammatory tissue and minimizing patientmorbidity.Although developed as a minimally invasive technique to avoid the morbidity of opensinus surgery, ESS still entails some degree of surgical trauma, postoperative pain,and inflammation. Intraoperative local anesthetic infiltration is routinelyperformed but is insufficient to control pain in the immediate postoperative period.Patients often require some form of systemic analgesia and this usually consists ofsome combination of acetaminophen, non‐steroidal anti‐inflammatory drugs (NSAIDs)such as ibuprofen, and opioids. However, there is currently no consensus in theliterature regarding the optimal analgesic regimen after ESS.Interestingly, in patients with aspirin‐exacerbated respiratory disease (AERD) atriad of asthma, CRS, and aspirin (ASA/NSAID sensitivity), NSAIDs are classicallyassociated with worsening of CRS symptoms. However, cyclooxygenase‐2 (COX‐2)inhibitors, a selective type of NSAID, have recently been studied as post‐ESSanalgesics and suggested as possible alternatives to opioids, which have many knownpotential adverse effects. These agents have also been studied for theiranti‐inflammatory properties in patients undergoing ESS and have been shown todecrease the levels of circulating prostaglandins in this population. Thus, AERDpatients are a particularly important population in which to assess the effect ofCOX‐2 inhibitors on post‐operative pain and inflammation. This randomized,prospective study will evaluate both the anti‐inflammatory and analgesic effects ofa COX‐2 inhibitor, celecoxib, in patients with AERD and CRS following endoscopicsinus surgery. The investigators hypothesize that supplementation with celecoxib canpotentially improve surgical outcomes and reduce the postoperative usage of opioidanalgesics without an increased risk of bleeding or asthma exacerbation. 2. The objectives of this study are: 1) to determine whether the addition of celecoxibto the FESS post‐operative analgesia regimen can alter subjective and objectiverecovery from CRS signs and symptoms, and 2) to determine whether the addition ofthe COX‐2 inhibitor, celecoxib, to the endoscopic sinus surgery post‐operativeanalgesia regimen can reduce the amount of opioid narcotic used by patients forbreakthrough pain. 3. Trial Design: The study is a prospective, double‐blinded, randomized controlledstudy and will be conducted at St. Joseph's Hospital in London, ON (CAN). There willbe two study arms with 1:1 allocation, one arm will receive the study treatment andthe other will receive a placebo; 4. Sample Size Calculation: The initial pre‐study sample size was calculated with 80%power at a significance level of 0.05. For the primary objective, previous studieshave established that a 40% difference on the Lund‐Kennedy Endoscopic Score would beclinically relevant. The statistical power was assumed to be 80%, and the neededsignificance level (2‐tailed alpha error) was assumed to be 5%. Based on theliterature, a mean difference of 3.4 and an SD of 2.6 for the Lund‐Kennedyendoscopic reporting system was used for calculation, giving a sample size of 22.For the secondary objective, the sample size was calculated as follows. Assuming adifference of 2 of mean pain score (with a standard deviation of 2) on the NumericRating scale as significant, a sample size of 16 in each group is required. It hasbeen reported elsewhere a total of 4.5 (+/‐4.4) milligram morphine equivalent forpatients undergoing a sinus surgery. To reduce this requirement to zero a samplesize of 12 in each group would be required. As such, the aim is to enrol 44 patientsto account for potential loss of follow‐up and ensure the study is appropriatelypowered. 5. Interventions: Patients in the treatment arm of the study will receive celecoxib 200mg PO BID for 7 days and patients in the control arm will receive placebo PO BID for7 days. Both medications are to be started on the evening of the day of surgery.Both groups will also be given a prescription for tramadol, an opioid medication, tobe used as needed for breakthrough pain. Specifically, tramadol 50 mg PO Q6H PRN x10 tablets will be prescribed. Patients will also be permitted to take acetaminophenfor breakthrough pain as needed and will be encouraged to use acetaminophen prior tonarcotic usage. Finally, all patients will be prescribed a nasal saline rinse whichis to be started on postoperative day one. 6. Randomization: Randomization will be via sequential random number generation from 1to 40. Medications will be prepared by the hospital pharmacy and will be randomizedin their preparation by the pharmacy. A master list will be kept in a sealedenvelope by the PI in order to break blinding if an emergency occurs. Both studyteam members and patients will remain blinded to the group until after the study iscompleted.