Ketorolac Versus Ibuprofen to Treat Painful Episodes of Sickle Cell Disease

Condition(s) targeted: Hematologic Diseases; Anemia, Sickle Cell

Intervention: Intravenous Ketorolac (Drug); Ibuprofen (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: National Heart, Lung, and Blood Institute (NHLBI)

Official(s) and/or principal investigator(s):
Charles T. Quinn, MD, Study Chair, Affiliation: University of Texas Southwestern Medical Center

The purpose of this study is to compare ketorolac, a potent, non-steroidal anti-inflammatory drug (NSAID), with ibuprofen, a commonly used NSAID, for the treatment of the painful crisis of sickle cell disease (SCD).

Official title: Ketorolac Versus Ibuprofen for the Painful Crisis of Sickle Cell Disease - Southwestern Comprehensive Sickle Cell Center

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Amount of time to a 50% reduction in reported pain intensity

Secondary outcome:

Duration of hospitalization

Amount of opioid use

Occurrence of azotemia

Fluid retention

Hematuria

Dyspepsia

Gastrointestinal ulceration

Bleeding

Detailed description: BACKGROUND:

SCD is a common disorder among African Americans and other minority groups. It is characterized by chronic anemia and episodic vaso-occlusive crises. The most common of these crises is the painful crisis. Current treatment of the painful crisis includes rest, hydration, and analgesic medication. Morphine is the most commonly prescribed analgesic medication for moderate to severe painful episodes, but there are several side effects associated with its use, including somnolence, respiratory depression, constipation, dysphoria, and pruritus. Other analgesic medications, including NSAIDs, may improve pain control and decrease the need for morphine and other opioid drugs; however, more research is needed to confirm the benefits in individuals with SCD.

DESIGN NARRATIVE:

This study will enroll 120 children who will receive standard opioid and supportive therapy. In addition to this care, participants will be randomly assigned to receive one of the following: 1) intravenous ketorolac and oral placebo; or 2) intravenous placebo and oral ibuprofen. Outcome assessments will include the duration of hospitalization for opioid therapy; the degree of pain intensity and relief determined by validated pain scales; and the utilization of opioid medications during hospitalization. All participants will be monitored for potential adverse effects of the study medications by laboratory measurements and clinical assessments. Additionally, participants will self-report pain levels using the Oucher pain scale. Participants will be monitored for the development of adverse events, including gastrointestinal symptoms and deterioration of kidney function, as determined by daily kidney function tests including BUN, creatinine, and hematuria.

Minimum age: 6 Years. Maximum age: 18 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Confirmed diagnosis of any form of SCD, including sickle cell anemia,

sickle-hemoglobin C disease, and sickle-ß˖ or ß°-thalassemia

- Currently experiencing an acute painful episode (vaso-occlusive crisis), defined as

acute pain in the extremities, back, abdomen, or chest that has lasted at least 4 hours and is presumed to be due to SCD, with no other identified cause

- Onset of severe pain in its current location(s) must have occurred within 72 hours of

study entry

- Intensity of pain must be great enough to necessitate hospitalization for opioid

analgesia (e. g., failure of home and outpatient therapy)

- Ability to comprehend and use patient-controlled analgesia (PCA)

- Score of 6 or greater on the baseline pain scale

Exclusion Criteria:

- Temperature greater than or equal to 38. 5ºC at the time of study entry or in the

preceding 12 hours

- Has a new lobar pulmonary infiltrate or a diagnosis of acute chest syndrome (i. e., a

new lobar pulmonary infiltrate and two or more of the following: temperature greater than 38ºC, tachypnea, dyspnea, intercostal or supraclavicular retractions, nasal flaring, chest wall pain, and an oxygen saturation of less than 90% in room air by pulse oximetry)

- Diagnosis of acute splenic or hepatic sequestration crisis (i. e., liver or spleen

enlarged from steady-state size and Hgb level decreased 2 g/dL or more from steady-state value)

- Currently experiencing priapism

- Pain caused by suspected or confirmed hepatobiliary disease (e. g., cholecystitis or

cholelithiasis)

- Chronic pain caused by suspected or confirmed aseptic or avascular necrosis of the

femoral or humeral heads

- Chronic pain syndrome characterized by opioid tolerance and defined by hospitalization

for at least 30 days for the management of pain in a 1 year period prior to study entry

- Current participation (last transfusion given within the 2 months prior to study

entry) in a program of chronic transfusions for the management of SCD; the use of hydroxyurea alone is permitted

- Allergy or history of anaphylactoid reactions to aspirin or other NSAIDs

- Kidney dysfunction (i. e., serum creatinine concentration greater than 1. 5 times the

upper limit of normal for age)

- History of gastrointestinal bleeding or ulceration requiring medical therapy

- Concomitant bleeding disorder (e. g., von Willebrand disease, hemophilia, or a

qualitative platelet defect)

- Any other medical condition that would make it unsafe to receive NSAIDs, as determined

by the study physician

- PCA not preferred

- Use of ketorolac in the 30 days prior to study entry

- Use of scheduled (e. g., "around the clock") opioid analgesics in the 5 days before the

onset of current acute painful crisis

- Pregnant

University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States; Recruiting
Charles T. Quinn, MD, Phone: 214-648-3896, Email: charles.quinn@utsouthwestern.edu
George R. Buchanan, MD, Phone: 214-648-8594, Email: george.buchanan@utsouthwestern.edu
Charles T. Quinn, MD, Principal Investigator
Zora R. Rogers, MD, Sub-Investigator
George R. Buchanan, MD, Sub-Investigator
Tim McCavit, MD, Sub-Investigator

Starting date: January 2005
Ending date: March 2008
Last updated: December 17, 2007