Clinical trial NCT03453541: Ketorolac Use in Pediatric Patients Undergoing Tonsillectomy
Official title: A Randomized, Double-blinded, Placebo-controlled Study of Ketorolac Use in Pediatric Patients Undergoing Tonsillectomy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Analgesic Adverse Reaction
Lead sponsor: Albany Medical College
Sponsor class: OTHER
First posted: 2018-03-05
Enrollment: 214
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This prospective, randomized, double blinded study is designed to compare the bleeding rates of ketorolac vs. placebo when used for post tonsillectomy pain control in pediatric patients ages 2-18.

Detailed description: Tonsillectomy/adenoidectomy is an elective operation, mainly in the pediatric population. This procedure is performed by Dr. Jason Mouzakes and the otolaryngology residents under his supervision. The location of the research is at the Albany Medical Center Hospital, Main Campus and South Clinical Campus. Duration of this study for each individual patient will be set at 14 days post procedure, taking into account that bleeding risk with this procedure is highest within the first 2 weeks post-operatively. Data will be obtained within 90 days after discharge from the hospital by telephone interview with the parents or hospital record. The investigators plan to enroll at least 600 patients, 300 in each group, ASA physical status I to III and age 2 years to 18 years old (inclusive). Parents and children may be informed about the study at the time when surgery is planned during initial office visit. Enrollment in the study will be done on the day of the surgery, after the Anesthesiologist or Otolaryngology/Anesthesiology Resident explains the purpose, benefits and possible risks of the study and answers all questions of the parents. Before enrollment is finalized, informed consent and informed assent, if applicable, to take part in a human research study will be obtained.

At the completion of surgery, patients will be transferred to the post-anesthesia care unit (PACU). Additional pain medication if needed in the PACU will be acetaminophen 15mg/kg oral solution or opioid medications at discretion of treating anesthesiologist. Acetaminophen will only be given in PACU if it was not received pre-operatively. Patients will be discharged to home from the PACU or 2nd level short-stay recovery unit (at South Clinical Campus) when standard criteria are met for each patient per protocol.

Randomization Plan:

Patients will be randomized by a card system. There will be 600 cards with 300 labeled (K) for ketorolac group and 300 labeled (NS) for placebo group along with the assigned subject number. Preservative free 0.9% normal saline will be used as placebo. Randomization will be done using www.randomization.com which will generate a randomization sequence with a concealed blocking schedule. A non-investigator will prepare envelopes numbered sequentially, each containing a card indicating the subject number (sequentially numbered 1 - 600) and group as randomized by above plan. Envelopes are opened only upon obtaining consent maintaining allocation concealment until treatment is initiated. Patients are therefore assigned a subject number at the initiation of the study. The non-treating anesthesiologist will open the next sequential envelope (starting from envelope #1) and draw up the specified drug and give the drug with a patient label to the treating anesthesiologist. The non-treating anesthesiologist will also tell the treating anesthesiologist the patient's subject number so it may be recorded on the individual data collection sheet. The non-treating anesthesiologist will place a patient label on the drug card and store the card in the anesthesiology office, specifically Dr Afroze's office inside of room D108. Dr Afroze's office is locked and has minimal access. The patient drug cards will be accessed by the research team two weeks after the surgery date to record patient data.

The PACU nurses, surgeon, residents, and treating anesthesiologist will all be blinded and may perform the PACU scoring and data collection. Study drugs will be documented the same exact way on the anesthesia records for all the study patients. All the study patients' charts will have both drugs documented as IN study drug dose in mg. The doses of the drugs are pre-calculated based on the patient's weight and will be drawn by a non-treating anesthesiologist and administered by the treating anesthesiologist at the time of the surgery.

Patients for our study will be recruited from the Pediatric ENT clinical practice of Dr. Mouzakes. Surgery, anesthesia, and postoperative recovery will take place at the Albany Medical Center Hospital, Main Campus and South Clinical Campus. The investigators plan to enroll 600 children, age of 2 to 18 years old (inclusive) and ASA physical status I to III. The investigators anticipate completing our study in 12 to 24 months.

This study will have power of 81% to show that the bleeding rate for new treatment (ketorolac) is at least as low as the event rate for the control group. This assumes that the true event rates for the active control and new treatment populations are precisely equal (at 2.0%), that a difference of 3.0% or less is unimportant, that the sample size in the two groups will be 280 and 280, and that alpha (1 tailed) is set at .05.

Formally, the null hypothesis is that the event rate for new treatment is 3.0 percentage points higher than the event rate for active control, and the study has power of 81.3% to reject this null. Equivalently, the likelihood is 81.3% that the 95.0% confidence interval for the difference in event rates will exclude a 3.0 point difference in favor of active control.

The primary endpoint, bleeding rates, will be compared between the two groups by Chi-square test (or Fisher's exact test if expected values are 5 or less). Other secondary categorical data (readmission, PACU nausea/vomitting) will be analyzed similarly. Continuous data (opioid administrations, PACU pain scores, length of stay in recovery units) will be compared with an independent sample t-test or Mann-Whitney test if data demonstrates significant non-normality. Multivariable analysis will be used to determine if bleeding is associated with the covariates age, gender, weight, ASA status, and primary or secondary diagnoses.

The risks of the study include the risks of possible allergic reactions to ketorolac in patients with no previously known drugs allergies, and possible decreased pain control for some patients. However, as is standard of practice, all patients with uncontrolled post-operative pain will have additional acetaminophen or opioid medications administered as needed for pain in the post-operative units under the guidance of the treating anesthesiologist. As previously demonstrated, ketorolac intravenous \& intramuscular have been shown in the anesthesiology literature to be safe with a low incidence of side effects. Patient's parents will be informed of other possible side effects of ketorolac including platelet dysfunction with prolonged bleeding at operative site, gastrointestinal bleeding, and renal dysfunction. There are no described long term side effects from single intraoperative application of ketorolac. Side-effects that have been noticed in other studies are minimal and transient. Patient's parents will have access to the investigator and ER department 24 hours a day, 7 days a week if any concerns appear.

The major benefit from IV ketorolac for patients is potential of adequate pain control for tonsillectomy with decreased use of opioid analgesia, ameliorating possible negative side effects of narcotics such as respiratory depression and nausea/vomiting. Achieving adequate pain control in tonsillectomy patients leads to improved oral intake and decreased risk of dehydration. Additionally, results of this study will be contributing to improvement in pain management for future patients undergoing tonsillectomy surgery. Overall, The investigators feel that the risks involved with this study are minimal and potential benefits are quite large.

The PHI to be collected includes the medical record number and date of birth to identify the range of age of the participants, possible allergy to medications, and brief past medical history relevant to the study.

If consent is not obtained, the patient will not be included in the study and will receive standard assessment and care, which typically includes single dose 0.5mg/ kg ketorolac at the completion of the procedure and additional pain medications in recovery areas as needed, such as acetaminophen or opioids. At any point in the study, the subject may choose to discontinue participation and opt for standard treatment.

Eligibility criteria: Inclusion Criteria:

-ASA physical status I to III, age of 2 years to 18 years old (inclusive) scheduled for elective tonsillectomy with or without adenoidectomy.

Exclusion Criteria:

-Exclusion criteria are: allergy to any nonsteroidal anti-inflammatory medications, bleeding disorders, history of gastrointestinal bleeding, renal impairment, severe asthma, cardiac/hepatic disease, use of anticoagulation, recent NSAID use (within last 72 hours) or any other medical problem that in the opinion of investigator would interfere with study participation.

Primary outcomes:
measure: Rebleeding rate requiring operative intervention
timeFrame: 2 weeks post-operative
Secondary outcomes:
measure: PACU length of stay
timeFrame: Immediately after operation
measure: Post-operative opioid dosage
timeFrame: Immediately after operation
measure: Post-operative pain score
timeFrame: Immediately after operation
measure: Presence of post-operative nausea/vomiting
timeFrame: Immediately after operation
measure: Number of emergency room visits/admissions
timeFrame: 2 weeks post-operative
Other outcomes:
Locations:
city: Albany
country: United States
facility: Albany Medical Center
state: New York
Study officials:
affiliation: Albany Medical College
name: Farzana Afroze, MD
role: PRINCIPAL_INVESTIGATOR
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