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Congenital Heart Disease in ChildrenPhase 4CIVIKNCT04040452

Continuous vs Intermittent Ketorolac for Pain Control in Peds CV Surgery

A Phase 4 study testing Continuous ketorolac in people with Congenital Heart Disease in Children, run by Phoenix Children's Hospital at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 3 to 59 months
Conditions the study is for
Congenital Heart Disease in Children
What is being tested?
Continuous ketorolac
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
166 participants
Where
1 siteUnited States
Study dates
1 Mar 2021to 1 Dec 2027
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 59 months
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Kevin Engelhardt, MD contact

6029333366

kengelhardt@phoenixchildrens.com

Samantha Stack, BS contact

6029330607

sstack@phoenixchildrens.com

United States1 site, 1 recruiting
  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016

    Kevin Engelhardt, MD, 6029333366, kengelhardt@phoenixchildrens.com

    Samantha Stack, BS, 6029330607, sstack@phoenixchildrens.com

    Recruiting

Other trials in United States

About this study

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

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.

Read the 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 72 hours post-operatively.

Being tested
Continuous ketorolac
Keywords
pain control, cardiac surgery, pediatric, opioid, NSAID, congenital heart disease
Medical subject headings
Agnosia, Heart Defects, Congenital

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Continuous ketorolacDrug

    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.

Study groups in NCT04040452
Study groupRoleWhat they receive
TreatmentExperimental1. 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.
Receives: Drug: Continuous ketorolac
Standard of carePlacebo comparator1. 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)
Receives: Drug: Continuous ketorolac

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Within 72 hours of cardiac surgery

Secondary outcomes (5)
  1. 1. Total fentanyl equivalents received in each 24 hour period before and after initiating the study drug

    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).

    Measured: Within 72 hours after cardiac surgery

  2. Rate of acute kidney injury measured by pRIFLE criteria

    Acute kidney injury rates

    Measured: Within 72 hours after cardiac surgery

  3. Major bleeding events

    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

    Measured: Within 72 hours after cardiac surgery

  4. Pain scores

    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

    Measured: Within 72 hours after cardiac surgery

  5. Sedative agent requirements

    Dose receipt/drug selection of sedative agents

    Measured: Within 72 hours after cardiac surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jul 2019
  2. Study start1 Mar 2021
  3. Primary completion1 Oct 2027 (estimated)
  4. Study completion1 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized, placebo-controlled
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
166 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04040452
Sponsor's protocol ID
19-554
Acronym
CIVIK
Status last verified
Jul 2026
First submitted
29 Jul 2019
Last updated
12 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: We do not plan to make IPD available to other researchers.

Publications

  • Onaka T, Yagi K. Differential effects of naloxone on neuroendocrine responses to fear-related emotional stress. Exp Brain Res. 1990;81(1):53-8. doi: 10.1007/BF00230100.

    PubMed 2168320
  • Burd RS, Tobias JD. Ketorolac for pain management after abdominal surgical procedures in infants. South Med J. 2002 Mar;95(3):331-3.

    PubMed 11902701
  • 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.

    PubMed 1911008
  • 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.

    PubMed 21233498
  • 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.

    PubMed 19134246
  • 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.

    PubMed 23058854
  • 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.

    PubMed 15365927
  • 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.

    PubMed 27580638
  • 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.

    PubMed 8970395
  • 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.

    PubMed 19562323
  • 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.

    PubMed 24441450
  • 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.

    PubMed 16618297

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Continuous ketorolac in people with Congenital Heart Disease in Children, run by Phoenix Children's Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Kevin Engelhardt, MD (6029333366, kengelhardt@phoenixchildrens.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

1. Total fentanyl dose equivalents received within the first 96 hours post-operatively (time frame: Within 72 hours of cardiac surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04040452, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2026.

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