Ketorolac Versus Ibuprofen to Treat Painful Episodes of Sickle Cell Disease - Full Text View

Sponsored by:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00115336

Purpose

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).

Condition	Intervention	Phase
Hematologic Diseases Anemia, Sickle Cell	Drug: Intravenous Ketorolac Drug: Ibuprofen	Phase IV

Genetics Home Reference related topics: sickle cell disease

MedlinePlus related topics: Anemia Sickle Cell Anemia

Drug Information available for: Ibuprofen Dexibuprofen Ketorolac Ketorolac tromethamine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Ketorolac Versus Ibuprofen for the Painful Crisis of Sickle Cell Disease - Southwestern Comprehensive Sickle Cell Center

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Duration of hospitalization [ Time Frame: Measured during hospitalization ] [ Designated as safety issue: No ]
Amount of opioid use [ Time Frame: Measured during hospitalization ] [ Designated as safety issue: No ]
Occurrence of azotemia [ Time Frame: Measured during hospitalization ] [ Designated as safety issue: Yes ]
Fluid retention [ Time Frame: Measured during hospitalization ] [ Designated as safety issue: Yes ]
Hematuria [ Time Frame: Measured during hospitalization ] [ Designated as safety issue: Yes ]
Dyspepsia [ Time Frame: Measured during hospitalization ] [ Designated as safety issue: Yes ]
Gastrointestinal ulceration [ Time Frame: Measured during hospitalization ] [ Designated as safety issue: Yes ]
Bleeding [ Time Frame: Measured during hospitalization ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	120
Study Start Date:	January 2005
Estimated Study Completion Date:	December 2008
Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Intravenous ketorolac and oral placebo	Drug: Intravenous Ketorolac Intravenous ketorolac
2: Active Comparator Intravenous placebo and oral ibuprofen	Drug: Ibuprofen Ibuprofen, taken orally

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.

Eligibility

Ages Eligible for Study:	6 Years to 18 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00115336

Locations

United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Study Chair:

Charles T. Quinn, MD

University of Texas Southwestern Medical Center

More Information

Responsible Party:	U.T. Southwestern Medical Center Dallas ( Charles T. Quinn, M.D. )
Study ID Numbers:	191, U54 HL70588
Study First Received:	June 21, 2005
Last Updated:	August 25, 2008
ClinicalTrials.gov Identifier:	NCT00115336
Health Authority:	United States: Federal Government

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

Blood Diseases
Sickle Cell Anemia

Study placed in the following topic categories:

Ibuprofen
Hematologic Diseases
Ketorolac
Anemia
Anemia, Hemolytic
Pain
Sickle cell anemia

Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Hemoglobinopathies
Hemoglobinopathy
Ketorolac Tromethamine
Anemia, Sickle Cell

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Pharmacologic Actions
Analgesics, Non-Narcotic

Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009