Celecoxib After Tonsillectomy

Phase 2

Completed

Conditions: Tonsillectomy

Interventions: Other: Placebo
Drug: Celecoxib
Drug: Acetaminophen
Drug: Oxycodone

Registration Number: NCT02934191

Lead Sponsor: Children's Hospital of Philadelphia

Brief Summary: Tonsillectomy is one of the most common pediatric surgical procedures in the United States. Postoperative pain is substantial, with typical regimens employing narcotic derivatives and acetaminophen for 1-2 weeks after surgery. Recent enthusiasm for use of ibuprofen as an alternative has been tempered by equivocal data on its relative safety in regard to risk of postoperative hemorrhage. The primary objective is to evaluate efficacy of celecoxib for pain control after tonsillectomy in children. The secondary objective is to assess safety in regard to postoperative hemorrhage and adverse events.

Detailed Description: This is a randomized, double-blind, placebo-controlled trial. Subjects will take acetaminophen plus either celecoxib or placebo in regular scheduled doses, and will supplement as needed with standard of care analgesic therapy (oxycodone/acetaminophen).

Celecoxib is approved by the FDA for use in children ages 2 and older for treatment of juvenile rheumatoid arthritis (JRA). Celecoxib is on the Children's Hospital of Philadelphia (CHOP) formulary for use in (1) patients \>= 2 years old for JRA, (2) patients \>= 12 years old and \>=40 kg who have increased risk for gastrointestinal (GI) adverse effects or bleeding concerns precluding use of traditional nonsteroidal anti-inflammatory drugs (NSAIDs), and (3) oncology patients with surface area \>= 0.4 square meters for anti-angiogenesis. Celecoxib is approved by the FDA for use in adults for treatment of arthritic conditions, acute/ postoperative pain, and primary dysmenorrhea, and has been widely used since its introduction in 1998.

Setting/Participants:Subjects are healthy children aged 3 to 11 years who undergo tonsillectomy with or without adenoidectomy at any Children's Hospital of Philadelphia (CHOP) location. Subjects with coagulation disorders are excluded. Approximately 300 subjects will be enrolled, 150 in each treatment group.

Study Interventions and Measures: Subjects are provided celecoxib or placebo in scheduled doses every 12 hours for 5 days, then continue until they are pain-free, for a maximum of 10 days. Throughout the study, they are allowed to use oxycodone/acetaminophen as needed for additional pain control, following standard clinical care. Acetaminophen is used around the clock for the first 5 days in all subjects. For 14 days following surgery, subjects record pain levels on validated pain scale instruments, quantity of narcotic medication and acetaminophen required, and time to return to normal diet. All Emergency Department and hospital admissions during the 30 postoperative days are recorded, noting incidence of excess pain, dehydration, hemorrhage, and other complications.

Pain control efficacy is assessed by comparing groups for number of days in which narcotic medication was used, and total quantity of rescue pain medication consumed. Rates of hospital readmission and postoperative hemorrhage, and the need for operative control, are also compared between groups.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 172

Inclusion Criteria

Males and females age 3 to 11 years inclusive.
Scheduled to undergo tonsillectomy (with or without adenoidectomy).
Weight ≥10 kg.
Girls ≥ 11 years of age must have a negative urine/serum pregnancy test on the day of surgery and must use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the study.
Parental/guardian permission (informed consent) and if appropriate, child assent.

Exclusion Criteria

Prior adenotonsillar surgery.
Concomitant surgical procedure that adds more than mild additional pain. Note: ear tubes are always permissible.
Coagulation disorder, or any other hematologic disorder that affects clotting or results in anemia.
Moderate to severe asthma, defined as subjects who either (1) have daily symptoms requiring daily use of short-acting bronchodilators, or (2) had an exacerbation in the last 3 months requiring admission, emergency department (ED) visit, or systemic corticosteroid administration.
Any degree of aspirin-sensitive asthma, or any history of asthma exacerbation caused by NSAID use.
Severe obstructive sleep apnea, defined as an obstructive apnea-hypopnea index >30 per hour and/or lowest oxygen saturation below 80%
Significant chronic pulmonary disease, defined as subjects requiring oxygen therapy, ventilator support, or positive pressure therapy.
Significant cardiac disease, defined as any one of the following: cardiovascular disease, structural cardiac anomalies, prior cardiac surgery, or requirement for cardiac anesthesia.
Severely obese (weight or body mass index > 95th percentile for age) or underweight (weight <5th percentile for age).
History of hepatic or renal disease, or condition that impairs hepatic or renal function.
Juvenile rheumatoid arthritis (JRA).
History of GI bleeding, or chronic GI condition that would increase risk of bleeding, ulceration, or perforation
Hypertension.
Craniofacial syndromes.
Syndrome or neurologic condition that would hinder accurate assessment of postoperative pain.
Inability to feed orally or take oral pain medication.
Chronic pain disorders, or otherwise requiring pain medication more than once weekly.
Laboratory abnormalities on the preoperative complete blood count (CBC):
- Hemoglobin < 9 gm/dL
- Platelet count < 100,000/mm3
Any investigational drug use within 30 days prior to enrollment.
Pregnant or lactating females.
Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
Hypersensitivity or allergic reactions to celecoxib, aspirin, or other NSAIDs, including asthma flare ups
Allergy to sulfonamides or calcium carbonate.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Acetaminophen/Oxycodone + Placebo	Placebo	Subjects will take acetaminophen orally (dose 15mg/kg/dose) in scheduled doses every 4 hours for the first 5 days. Subjects will also take the placebo orally twice a day. The first dose of placebo will be given preoperatively, within 1 hour prior to entering the operating room. The second dose will be given at bedtime on the night of surgery and subsequent doses will be given 12 hours apart. Supplemental standard of care oxycodone may be used to control breakthrough pain.
Acetaminophen/Oxycodone + Celecoxib	Celecoxib	Subjects will take acetaminophen orally (dose 15mg/kg/dose) in scheduled doses every 4 hours for the first 5 days. Subjects will also take celecoxib orally (dose is 6mg/kg twice a day with a maximum dose of 300mg twice a day). The first dose of celecoxib will be given preoperatively, within 1 hour prior to entering the operating room. The second dose will be given at bedtime on the night of surgery and subsequent doses will be given 12 hours apart. Supplemental standard of care oxycodone may be used to control breakthrough pain.
Acetaminophen/Oxycodone + Celecoxib	Acetaminophen	Subjects will take acetaminophen orally (dose 15mg/kg/dose) in scheduled doses every 4 hours for the first 5 days. Subjects will also take celecoxib orally (dose is 6mg/kg twice a day with a maximum dose of 300mg twice a day). The first dose of celecoxib will be given preoperatively, within 1 hour prior to entering the operating room. The second dose will be given at bedtime on the night of surgery and subsequent doses will be given 12 hours apart. Supplemental standard of care oxycodone may be used to control breakthrough pain.
Acetaminophen/Oxycodone + Celecoxib	Oxycodone	Subjects will take acetaminophen orally (dose 15mg/kg/dose) in scheduled doses every 4 hours for the first 5 days. Subjects will also take celecoxib orally (dose is 6mg/kg twice a day with a maximum dose of 300mg twice a day). The first dose of celecoxib will be given preoperatively, within 1 hour prior to entering the operating room. The second dose will be given at bedtime on the night of surgery and subsequent doses will be given 12 hours apart. Supplemental standard of care oxycodone may be used to control breakthrough pain.
Acetaminophen/Oxycodone + Placebo	Acetaminophen	Subjects will take acetaminophen orally (dose 15mg/kg/dose) in scheduled doses every 4 hours for the first 5 days. Subjects will also take the placebo orally twice a day. The first dose of placebo will be given preoperatively, within 1 hour prior to entering the operating room. The second dose will be given at bedtime on the night of surgery and subsequent doses will be given 12 hours apart. Supplemental standard of care oxycodone may be used to control breakthrough pain.
Acetaminophen/Oxycodone + Placebo	Oxycodone	Subjects will take acetaminophen orally (dose 15mg/kg/dose) in scheduled doses every 4 hours for the first 5 days. Subjects will also take the placebo orally twice a day. The first dose of placebo will be given preoperatively, within 1 hour prior to entering the operating room. The second dose will be given at bedtime on the night of surgery and subsequent doses will be given 12 hours apart. Supplemental standard of care oxycodone may be used to control breakthrough pain.

Primary Outcome Measures

Name	Time	Method
Difference in Number of Days Requiring Rescue Pain Medication	2 weeks post-operative	The number of days on narcotic pain medication following surgery will be compared between the two treatment groups
Difference in Amount of Rescue Pain Medication Consumed	2 weeks post-operative	The total amount of rescue pain medication consumed in the 2-week postop period will be compared between the two treatment groups.

Secondary Outcome Measures