Continuous vs Intermittent Ketorolac for Pain Control in Peds CV Surgery

Sponsor

Phoenix Children's Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT04040452

Collaborator

(none)

166

Enrollment

Location

Arms

Anticipated Duration (Months)

6.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The proposed study will be a prospective, randomized, double blind, placebo controlled trial to compare the use of a continuous infusion versus intermittent ketorolac on postoperative patients in the pediatric cardiovascular ICU. We intend to determine if the continuous infusion leads to a decreased utilization of opiates when compared to intermittent ketorolac.

Condition or Disease	Intervention/Treatment	Phase
Congenital Heart Disease in Children	Drug: Continuous ketorolac	Phase 4

Detailed Description

The mainstay of postoperative pain control in the CVICU remains opiate-based therapy. Reliance on this class of medications can be detrimental, contributing to complications including hemodynamic instability, dependency, and withdrawal which can ultimately lead to longer hospital admissions, as well as long term and persistent neurodevelopmental effects. In addition, the opioid crisis has driven practitioners to aim for methods to reduce opioid exposure and post-operative narcotic prescriptions in pediatric and adult patients alike. There is a growing body of evidence in the adult literature showing promising results with the use of a continuous infusion of ketorolac in postoperative patients, including in a pediatric population. What the current literature has failed to show is whether a continuous infusion of ketorolac post operatively decreases the use of opiate mediations in a pediatric population compared to intermittent bolus injections, which is the current standard of care. Given the sensitivity and fragility inherent in those patients with CHD, working to reduce deleterious effects from excessive and prolonged opiate exposure is imperative. This study aims to examine whether the use of a continuous infusion of ketorolac can reduce the amount of opiates needed to treat postoperative pain control in the pediatric CVICU population, in comparison to patients who receive intermittent ketorolac within the first 96 hours post-operatively.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

166 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, placebo-controlledRandomized, placebo-controlled

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

Double-blind

Primary Purpose:

Supportive Care

Official Title:

Continuous Infusion Versus Intermittent Ketorolac for Postoperative Pain Control in Pediatric Cardiac Surgery Patients

Anticipated Study Start Date :

Sep 1, 2019

Anticipated Primary Completion Date :

Dec 1, 2020

Anticipated Study Completion Date :

Dec 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Description: Patients randomized for the treatment arm of the study group will receive a continuous infusion of ketorolac plus an intermittent dose of placebo (plasmalyte). To eliminate excess exposure and the associated side effects, all patients enrolled in the study will not be given any additional NSAIDs (except aspirin, which is standard of care in many post-operative cardiac surgery patients) during the study period. Dosage and Route of Administration: Continuous ketorolac 0.08mg/kg/hr, with a maximum of 5mg/hr for patients weighing greater than or equal to 60kg, administered intravenously by nursing staff. Study drug will infuse continuously for 48 hours. Intermittent Plasmalyte 0.033mL/kg (max 2mL) infusion every 6 hours for 48 hours.	Drug: Continuous ketorolac Patients randomized for the treatment arm of the study group will receive a continuous infusion of ketorolac plus an intermittent dose of placebo (plasmalyte) for 48 hours.
Placebo Comparator: Standard of care Description: Patients randomized to the standard of care arm of the study will receive a generically marked syringe of Plasmalyte to be infused at the same rate as the treatment medication, and will only receive intermittent dosing of ketorolac (current standard of care). As in the treatment group, no additional NSAIDs (except aspirin) are to be given during the 48 hour study period. Dosage and Route of Administration Continuous Plasmalyte infusion to match the aforementioned ketorolac dosing Intermittent ketorolac 0.5mg/kg IV infusion every 6 hours (max 30mg per dose)	Drug: Continuous ketorolac Patients randomized for the treatment arm of the study group will receive a continuous infusion of ketorolac plus an intermittent dose of placebo (plasmalyte) for 48 hours.

Arm

Intervention/Treatment

Experimental: Treatment

Description: Patients randomized for the treatment arm of the study group will receive a continuous infusion of ketorolac plus an intermittent dose of placebo (plasmalyte). To eliminate excess exposure and the associated side effects, all patients enrolled in the study will not be given any additional NSAIDs (except aspirin, which is standard of care in many post-operative cardiac surgery patients) during the study period. Dosage and Route of Administration: Continuous ketorolac 0.08mg/kg/hr, with a maximum of 5mg/hr for patients weighing greater than or equal to 60kg, administered intravenously by nursing staff. Study drug will infuse continuously for 48 hours. Intermittent Plasmalyte 0.033mL/kg (max 2mL) infusion every 6 hours for 48 hours.

Drug: Continuous ketorolac

Patients randomized for the treatment arm of the study group will receive a continuous infusion of ketorolac plus an intermittent dose of placebo (plasmalyte) for 48 hours.

Placebo Comparator: Standard of care

Description: Patients randomized to the standard of care arm of the study will receive a generically marked syringe of Plasmalyte to be infused at the same rate as the treatment medication, and will only receive intermittent dosing of ketorolac (current standard of care). As in the treatment group, no additional NSAIDs (except aspirin) are to be given during the 48 hour study period. Dosage and Route of Administration Continuous Plasmalyte infusion to match the aforementioned ketorolac dosing Intermittent ketorolac 0.5mg/kg IV infusion every 6 hours (max 30mg per dose)

Drug: Continuous ketorolac

Patients randomized for the treatment arm of the study group will receive a continuous infusion of ketorolac plus an intermittent dose of placebo (plasmalyte) for 48 hours.

Outcome Measures

Primary Outcome Measures

1. Total fentanyl dose equivalents received within the first 96 hours post-operatively [Within 96 hours of cardiac surgery]
The total opioid receipt (converted to fentanyl equivalents) administered to patients enrolled in the study within the first 96 hours after cardiac surgery.

Secondary Outcome Measures

1. Total fentanyl equivalents received in each 24 hour period before and after initiating the study drug [Within 96 hours after cardiac surgery]
The total opioid receipt (converted to fentanyl equivalents) administered to patients enrolled in the study within each 24 hour period after cardiac surgery (up to 96 hours post-operatively).
Rate of acute kidney injury measured by pRIFLE criteria [Within 96 hours after cardiac surgery]
Acute kidney injury rates
Major bleeding events [Within 96 hours after cardiac surgery]
Hemoglobin decrease > 2 g/dL, requirement of 2 or more units of PRBC's/whole blood, or development of symptomatic/clinically evident bleeding in any organ or compartment
Pain scores [Within 96 hours after cardiac surgery]
FLACC scores (face, legs, activity, cry, consolability): score of 0-10 (10 being most severe pain, 0 being least severe). 0 = relaxed/comfortable, 1-3 = mild discomfort, 4-6 = moderate pain, 7-10 = severe discomfort or pain or both
Sedative agent requirements [Within 96 hours after cardiac surgery]
Dose receipt/drug selection of sedative agents

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Months to 4 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

All patients aged 3 months to 4 years admitted post operatively to the CVICU during the 12 month time period during which the study will be ongoing
Initiation of study medication within the first 48 hours post-operatively

Exclusion Criteria:

Patients that have acute kidney injury, as defined by pRIFLE criteria.
History of allergy or sensitivity reaction to ketorolac or any NSAID medications.
Requiring mechanical circulatory support (ECMO) or continuous renal replacement therapy (CRRT) within the first 48 hours post-operatively
Orthotopic heart transplantation
Clinically significant bleeding