Clinical trial NCT00115336: Ketorolac Versus Ibuprofen to Treat Painful Episodes of Sickle Cell Disease
Official title: Ketorolac Versus Ibuprofen for the Painful Crisis of Sickle Cell Disease - Southwestern Comprehensive Sickle Cell Center
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Hematologic Diseases
Anemia, Sickle Cell
Keywords: Blood Diseases
Sickle Cell Anemia
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: University of Texas Southwestern Medical Center
First posted: 2005-06-22
Enrollment: 10
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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 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

Primary outcomes:
measure: Time to a 50% Reduction in Reported Pain Intensity
timeFrame: Measured every 4 hours during hospitalization, over a mean hospitalization duration of 81.5 hours.
Secondary outcomes:
measure: Duration of Hospitalization
timeFrame: The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.
measure: Total Parenteral Opioid Usage
timeFrame: The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.
measure: Occurrence of Azotemia
timeFrame: The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.
measure: Fluid Retention
timeFrame: The entire study period (daily assessments during hospitalization [mean of 81.5 hours] and once at the 30-day follow-up visit, over a mean of 33.4 days)
measure: Hematuria
timeFrame: The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.
measure: Dyspepsia
timeFrame: The entire study period (daily assessments during hospitalization [mean of 81.5 hours] and once at the 30-day follow-up visit, over a mean of 33.4 days)
measure: Gastrointestinal Ulceration
timeFrame: The entire study period (daily assessments during hospitalization [mean of 81.5 hours] and once at the 30-day follow-up visit, over a mean of 33.4 days)
measure: Bleeding
timeFrame: The entire study period (daily assessments during hospitalization [mean of 81.5 hours] and once at the 30-day follow-up visit, over a mean of 33.4 days)
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: University of Texas Southwestern Medical Center
name: Charles T. Quinn, MD
role: STUDY_CHAIR
References: