Ketorolac Versus Ibuprofen to Treat Painful Episodes of Sickle Cell Disease
Ketorolac Versus Ibuprofen to Treat Painful Episodes of Sickle Cell Disease
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).
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.
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