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

NCT ID: NCT06579703

Last Updated: 2024-08-30

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 102 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-30
• Study Completion Date: 2028-02-15

Brief 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.

Detailed 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.

Conditions

Sickle Cell Disease; Sickle Cell Crisis; Veno-occlusive Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Reduced dose Ketorolac Arm A

a reduced dose of Ketorolac, 15 mg/mL

Group Type: EXPERIMENTAL

Ketorolac

Intervention Type: DRUG

Randomized to a single dose of:

Arm A: 15 mg/mL (per mL) Arm B: 30 mg/mL (per mL)

Standard of care dose Ketorolac Arm B

standard of care dose of Ketorolac, 30mg/mL

Group Type: ACTIVE_COMPARATOR

Ketorolac

Intervention Type: DRUG

Randomized to a single dose of:

Arm A: 15 mg/mL (per mL) Arm B: 30 mg/mL (per mL)

Interventions

Ketorolac

Randomized to a single dose of:

Arm A: 15 mg/mL (per mL) Arm B: 30 mg/mL (per mL)

Intervention Type: DRUG

Other Intervention Names

Toradol

Eligibility Criteria

Inclusion Criteria

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

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

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Blood and Cancer Center at Dell Children's Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alicia Chang, MD

Role: PRINCIPAL_INVESTIGATOR

Director, Comprehensive Sickle Cell Center

Central Contacts

Rhea Robinson, RN, BSN

Role: CONTACT

Phone: 512-628-1902

Email: Rmrobinson@ascension.org

Ashley Sherrod, RN, BSN

Role: CONTACT

Phone: 512-628-1902

Email: APSherrod@ascension.org

References

Brandow AM, Carroll CP, Creary S, Edwards-Elliott R, Glassberg J, Hurley RW, Kutlar A, Seisa M, Stinson J, Strouse JJ, Yusuf F, Zempsky W, Lang E. American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain. Blood Adv. 2020 Jun 23;4(12):2656-2701. doi: 10.1182/bloodadvances.2020001851.

Reference Type: BACKGROUND

PMID: 32559294 (View on PubMed)

Shapiro BS. The management of pain in sickle cell disease. Pediatr Clin North Am. 1989 Aug;36(4):1029-45. doi: 10.1016/s0031-3955(16)36735-9.

Reference Type: RESULT

PMID: 2666928 (View on PubMed)

Jones SF, O'Donnell AM. Clinical pharmacology: traditional NSAIDs and Jones SF, O'Donnell AM. Clinical pharmacology: traditional NSAIDs and selective COX-2 inhibitors. In: Macintyre PE, Walker SM, Rowbotham DJ, et al, eds. Clinical Pain Management (Acute Pain). 2nd ed. London, England: Hodder & Stoughton Limited; 2008:79.

Reference Type: RESULT

Motov S, Yasavolian M, Likourezos A, Pushkar I, Hossain R, Drapkin J, Cohen V, Filk N, Smith A, Huang F, Rockoff B, Homel P, Fromm C. Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med. 2017 Aug;70(2):177-184. doi: 10.1016/j.annemergmed.2016.10.014. Epub 2016 Dec 16.

Reference Type: RESULT

PMID: 27993418 (View on PubMed)

Staquet MJ. A double-blind study with placebo control of intramuscular ketorolac tromethamine in the treatment of cancer pain. J Clin Pharmacol. 1989 Nov;29(11):1031-6. doi: 10.1002/j.1552-4604.1989.tb03274.x.

Reference Type: RESULT

PMID: 2689472 (View on PubMed)

Minotti V, Betti M, Ciccarese G, Fumi G, Tonato M, Del Favero A. A double-blind study comparing two single-dose regimens of ketorolac with diclofenac in pain due to cancer. Pharmacotherapy. 1998 May-Jun;18(3):504-8.

Reference Type: RESULT

PMID: 9620101 (View on PubMed)

Brown CR, Moodie JE, Wild VM, Bynum LJ. Comparison of intravenous ketorolac tromethamine and morphine sulfate in the treatment of postoperative pain. Pharmacotherapy. 1990;10(6 ( Pt 2)):116S-121S.

Reference Type: RESULT

PMID: 2082307 (View on PubMed)

Simckes AM, Chen SS, Osorio AV, Garola RE, Woods GM. Ketorolac-induced irreversible renal failure in sickle cell disease: a case report. Pediatr Nephrol. 1999 Jan;13(1):63-7. doi: 10.1007/s004670050565.

Reference Type: RESULT

PMID: 10100293 (View on PubMed)

Baddam S, Aban I, Hilliard L, Howard T, Askenazi D, Lebensburger JD. Acute kidney injury during a pediatric sickle cell vaso-occlusive pain crisis. Pediatr Nephrol. 2017 Aug;32(8):1451-1456. doi: 10.1007/s00467-017-3623-6. Epub 2017 Feb 25.

Reference Type: RESULT

PMID: 28238158 (View on PubMed)

Other Identifiers

Chang_pain in SCD

Identifier Type: -

Identifier Source: org_study_id