Official Title: “Ketorolac Versus Ibuprofen for the Painful Crisis of Sickle Cell Disease - Southwestern Comprehensive Sickle Cell 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).

Study Type: Interventional

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

Study Primary Completion Date: August 2008

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.

Intervention(s) in this Clinical Trial

• Drug: Intravenous Ketorolac
  • Intravenous ketorolac
• Drug: Ibuprofen
  • Ibuprofen, taken orally

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Intravenous ketorolac and oral placebo
• Active Comparator: 2
  • Intravenous placebo and oral ibuprofen

Primary Measures

• Amount of time to a 50% reduction in reported pain intensity
  • Time Frame: Measured by pain intensity scales obtained every 4 hours during hospitalization
    Safety Issue?: No

Secondary Measures

• Duration of hospitalization
  • Time Frame: Measured during hospitalization
    Safety Issue?: No
• Amount of opioid use
  • Time Frame: Measured during hospitalization
    Safety Issue?: No
• Occurrence of azotemia
  • Time Frame: Measured during hospitalization
    Safety Issue?: Yes
• Fluid retention
  • Time Frame: Measured during hospitalization
    Safety Issue?: Yes
• Hematuria
  • Time Frame: Measured during hospitalization
    Safety Issue?: Yes
• Dyspepsia
  • Time Frame: Measured during hospitalization
    Safety Issue?: Yes
• Gastrointestinal ulceration
  • Time Frame: Measured during hospitalization
    Safety Issue?: Yes
• Bleeding
  • Time Frame: Measured during hospitalization
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 6 Years

Maximum Age for this Clinical Trial: 18 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Overall Clinical Trial Officials and Contacts

Charles T. Quinn, MD Study Chair University of Texas Southwestern Medical Center  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00115336

Study ID Number: 191

ClinicalTrials.gov Identifier: NCT00115336

Health Authority: United States: Federal Government