Continuous vs Intermittent Ketorolac for Pain Control in Peds CV Surgery

NCT04040452 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 166166
• Study Type: interventional
• Target: 166
• Locations: 1 country
• Sites: 1

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.

Conditions

Congenital Heart Disease in Children

Keywords

pain control; cardiac surgery; pediatric; opioid; NSAID; congenital heart disease

Outcome Measures

Primary Outcomes (1)

• 1. Total fentanyl dose equivalents received within the first 96 hours post-operatively

  The total opioid receipt (converted to fentanyl equivalents) administered to patients enrolled in the study within the first 96 hours after cardiac surgery.

  Within 72 hours of cardiac surgery

Secondary Outcomes (5)

• 1. Total fentanyl equivalents received in each 24 hour period before and after initiating the study drug

  Within 72 hours after cardiac surgery

• Rate of acute kidney injury measured by pRIFLE criteria

  Within 72 hours after cardiac surgery

• Major bleeding events

  Within 72 hours after cardiac surgery

• Pain scores

  Within 72 hours after cardiac surgery

• Sedative agent requirements

  Within 72 hours after cardiac surgery

Study Arms (2)

Treatment

EXPERIMENTAL

1. 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. 2. Dosage and Route of Administration: 1. 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. 2. Intermittent Plasmalyte 0.033mL/kg (max 2mL) infusion every 6 hours for 48 hours.

Drug: Continuous ketorolac

Standard of care

PLACEBO COMPARATOR

1. 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. 2. Dosage and Route of Administration 1. Continuous Plasmalyte infusion to match the aforementioned ketorolac dosing 2. Intermittent ketorolac 0.5mg/kg IV infusion every 6 hours (max 30mg per dose)

Drug: Continuous ketorolac

Interventions

Continuous ketorolac DRUG

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.

Standard of care; Treatment

Eligibility Criteria

• Age: 3 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• All patients aged 3 months to 4 years 11months admitted post operatively to the CVICU during the time period in which the study will be ongoing
• Initiation of study medication within the first 12-24 hours post-operatively
• The cardiovascular attending of record after review of the intraoperative course and post-operative laboratories determines the patient will receive Ketorolac for pain control

You may not qualify if:

• Patients that have acute kidney injury, as defined by the letter "I" in the 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
• Patients with known pre-operative medical renal disease, renal transplantation history, congenital or acquired renal abnormality or deformity

Sponsors & Collaborators

• Phoenix Children's Hospital: lead

Study Sites (1)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

RECRUITING

Related Publications (12)

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  PMID: 2168320 BACKGROUND

• Burd RS, Tobias JD. Ketorolac for pain management after abdominal surgical procedures in infants. South Med J. 2002 Mar;95(3):331-3.

  PMID: 11902701 BACKGROUND

• Burns JW, Aitken HA, Bullingham RE, McArdle CS, Kenny GN. Double-blind comparison of the morphine sparing effect of continuous and intermittent i.m. administration of ketorolac. Br J Anaesth. 1991 Sep;67(3):235-8. doi: 10.1093/bja/67.3.235.

  PMID: 1911008 BACKGROUND

• Cohen MN, Christians U, Henthorn T, Vu Tran Z, Moll V, Zuk J, Galinkin J. Pharmacokinetics of single-dose intravenous ketorolac in infants aged 2-11 months. Anesth Analg. 2011 Mar;112(3):655-60. doi: 10.1213/ANE.0b013e3182075d04. Epub 2011 Jan 13.

  PMID: 21233498 BACKGROUND

• Dawkins TN, Barclay CA, Gardiner RL, Krawczeski CD. Safety of intravenous use of ketorolac in infants following cardiothoracic surgery. Cardiol Young. 2009 Feb;19(1):105-8. doi: 10.1017/S1047951109003527. Epub 2009 Jan 12.

  PMID: 19134246 BACKGROUND

• Grimsby GM, Conley SP, Trentman TL, Castle EP, Andrews PE, Mihalik LA, Hentz JG, Humphreys MR. A double-blind randomized controlled trial of continuous intravenous Ketorolac vs placebo for adjuvant pain control after renal surgery. Mayo Clin Proc. 2012 Nov;87(11):1089-97. doi: 10.1016/j.mayocp.2012.07.018. Epub 2012 Oct 8.

  PMID: 23058854 BACKGROUND

• Gupta A, Daggett C, Drant S, Rivero N, Lewis A. Prospective randomized trial of ketorolac after congenital heart surgery. J Cardiothorac Vasc Anesth. 2004 Aug;18(4):454-7. doi: 10.1053/j.jvca.2004.05.024.

  PMID: 15365927 BACKGROUND

• Howard ML, Isaacs AN, Nisly SA. Continuous Infusion Nonsteroidal Anti-Inflammatory Drugs for Perioperative Pain Management. J Pharm Pract. 2018 Feb;31(1):66-81. doi: 10.1177/0897190016665539. Epub 2016 Aug 31.

  PMID: 27580638 BACKGROUND

• Britton J, Martinez FD. The relationship of childhood respiratory infection to growth and decline in lung function. Am J Respir Crit Care Med. 1996 Dec;154(6 Pt 2):S240-5. doi: 10.1164/ajrccm/154.6_Pt_2.S240. No abstract available.

  PMID: 8970395 BACKGROUND

• Inoue M, Caldarone CA, Frndova H, Cox PN, Ito S, Taddio A, Guerguerian AM. Safety and efficacy of ketorolac in children after cardiac surgery. Intensive Care Med. 2009 Sep;35(9):1584-92. doi: 10.1007/s00134-009-1541-1. Epub 2009 Jun 27.

  PMID: 19562323 BACKGROUND

• Jalkut MK. Ketorolac as an analgesic agent for infants and children after cardiac surgery: safety profile and appropriate patient selection. AACN Adv Crit Care. 2014 Jan-Mar;25(1):23-30; quiz 31-2. doi: 10.1097/NCI.0000000000000002.

  PMID: 24441450 BACKGROUND

• Moffett BS, Wann TI, Carberry KE, Mott AR. Safety of ketorolac in neonates and infants after cardiac surgery. Paediatr Anaesth. 2006 Apr;16(4):424-8. doi: 10.1111/j.1460-9592.2005.01806.x.

  PMID: 16618297 BACKGROUND

MeSH Terms

Conditions

Agnosia; Heart Defects, Congenital

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Kevin Engelhardt, MD

  Heart Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kevin Engelhardt, MD

CONTACT

6029333366; kengelhardt@phoenixchildrens.com

Samantha Stack, BS

CONTACT

6029330607; sstack@phoenixchildrens.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, placebo-controlled

Study Record Dates

• First Submitted: July 29, 2019
• First Posted: July 31, 2019
• Study Start: March 1, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)