Ketorolac Versus Ibuprofen to Treat Painful Episodes of Sickle Cell Disease

NCT00115336 | Terminated Phase 4 Results DMC

• 2 other identifiers: 191U54HL070588
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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).

Conditions

Hematologic Diseases; Anemia, Sickle Cell

Keywords

Blood Diseases; Sickle Cell Anemia

Outcome Measures

Primary Outcomes (1)

• Time to a 50% Reduction in Reported Pain Intensity

  The primary endpoint is the time to a 50% reduction in reported pain intensity. This endpoint is relative to the baseline pain intensity rating on the Oucher scale (minimum 0, maximum 10; higher scores indicate greater pain). The endpoint will be reached when the reported pain intensity is at least one-half of the baseline value on two consecutive measurements at least 4 hours apart. The time ascribed to the endpoint will be the time of the second of these two consecutive pain scales. Participants who do not have a 50% reduction in reported pain intensity, as defined above, before discharge from the hospital will be censored at the time of last rating on the Oucher pain scale before discharge from the hospital

  Measured every 4 hours during hospitalization, over a mean hospitalization duration of 81.5 hours.

Secondary Outcomes (8)

• Duration of Hospitalization

  The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.

• Total Parenteral Opioid Usage

  The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.

• Occurrence of Azotemia

  The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.

• Fluid Retention

  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)

• Hematuria

  The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.

Study Arms (2)

1-Intravenous ketorolac and oral placebo

ACTIVE COMPARATOR

Intravenous ketorolac and oral placebo

Drug: Intravenous Ketorolac

2-Intravenous placebo and oral ibuprofen

ACTIVE COMPARATOR

Intravenous placebo and oral ibuprofen

Drug: Ibuprofen

Interventions

Intravenous Ketorolac DRUG

Intravenous ketorolac

Also known as: Toradol

1-Intravenous ketorolac and oral placebo

Ibuprofen DRUG

Ibuprofen, taken orally

Also known as: Motrin, Advil

2-Intravenous placebo and oral ibuprofen

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• University of Texas Southwestern Medical Center: collaborator

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Hematologic Diseases; Anemia, Sickle Cell

Interventions

Ketorolac Tromethamine; Ibuprofen

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Limitations and Caveats

Extremely slow accrual led to the trial closing in 2008. Because less than 10% of planned enrollment was achieved, no statistical analysis of the primary or secondary outcome data was performed because of lack of power and generalizability.

Results Point of Contact

• Title: Dr. Charles Quinn
• Organization: Cincinnati Children's Hospital Medical Center

charles.quinn@cchmc.org

5138033086

Study Officials

• Charles T. Quinn, MD

  University of Texas Southwestern Medical Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2005
• First Posted: June 22, 2005
• Study Start: January 1, 2005
• Primary Completion: August 1, 2008
• Study Completion: December 1, 2008
• Last Updated: October 8, 2020
• Results First Posted: October 8, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)