Ketorolac for Acute Vaso-Occlusive Crisis in Pediatric Sickle Cell Disease

Last updated: August 28, 2024
Sponsor: Children's Blood and Cancer Center at Dell Children's Medical Center
Overall Status: Active - Not Recruiting

Phase

4

Condition

Sickle Cell Disease

Red Blood Cell Disorders

Treatment

Ketorolac

Clinical Study ID

NCT06579703
Chang_pain in SCD
  • Ages 1-21
  • All Genders

Study Summary

Pediatric patients who present with acute vaso-occlusive pain crisis may have equivalent pain reduction scores at lower dosing of intravenous Ketorolac compared to standard dosing of 0.5 mg/kg/dose IV (<16yo max 15mg, >16yo max 30mg) x 1 dose.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Pediatric patients with sickle cell disease (any genotype) who present to DCMCEmergency department or outpatient hematology clinic with acute pain.

Exclusion

Exclusion Criteria:

  • Patients receiving NSAID medication <6 hours from presentation

  • known kidney injury

  • sickle nephropathy

  • bleeding concerns

  • allergy to NSAID medication

  • chronic pain patient

  • hemodynamic instability as defined by the treating provider

Study Design

Total Participants: 102
Treatment Group(s): 1
Primary Treatment: Ketorolac
Phase: 4
Study Start date:
September 30, 2024
Estimated Completion Date:
February 15, 2028

Study Description

Sickle Cell Disease is characterized by a point mutation that causes red cell polymerization and clinically results in pain events, called vaso-occlusive crises (VOC), and end organ damage. VOC is the most common reason for hospital admissions and ER visits in the SCD population. Ketorolac is an NSAID class medication widely used for pain. Ketorolac reversibly inhibits cyclooxygenase-1 and cyclooxygenase-2 and inhibits the formation of prostaglandins and thromboxane. Specifically, in the SCD pediatric population, Ketorolac was shown to provide adequate pain relief without the need for additional IV analgesics in 50% of patients presenting to the emergency department with VOC. Despite its potential benefits, adverse effects from Ketorolac at standard dosing include gastrointestinal hemorrhage, nephrotoxicity and drug-drug interactions, some of which are dose-dependent. Patients with SCD may be particularly vulnerable to acute kidney injury from nephrotoxic medications given the propensity for chronic kidney disease from ongoing anemia, hemolysis and inflammation. A retrospective review in hospitalized patients with SCD who received at least one dose of ketorolac found that higher doses of ketorolac was a risk factor for acute kidney injury. In addition, a case report on a pediatric patient with SCD showed irreversible renal failure and bleeding complications after administration of ketorolac, despite adequate hydration. The American Society of Hematology guidelines for management of acute and chronic pain in patients with sickle cell disease recommend a short course of NSAIDs in addition to opioids for acute pain management based on very low certainty of evidence.

Several adult studies have suggested that the efficacy of ketorolac analgesia at 10mg is equivalent to higher doses (15mg-90mg) for treatment of various pain syndromes in the ED setting, post-operative and cancer pain. However, these studies excluded patients with SCD whose pain mechanism and pain thresholds may differ from these populations.

The investigators propose a prospective, randomized, double blind clinical trial that will take place in the DCMC Emergency Department and Children's Blood and Cancer Center Hematology Outpatient clinic.