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Ketorolac Versus Ibuprofen to Treat Painful Episodes of Sickle Cell Disease

Primary Purpose

Hematologic Diseases, Anemia, Sickle Cell

Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Intravenous Ketorolac
Ibuprofen
Sponsored by
Children's Hospital Medical Center, Cincinnati
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematologic Diseases focused on measuring Blood Diseases, Sickle Cell Anemia

Eligibility Criteria

6 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Texas Southwestern Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

1-Intravenous ketorolac and oral placebo

2-Intravenous placebo and oral ibuprofen

Arm Description

Intravenous ketorolac and oral placebo

Intravenous placebo and oral ibuprofen

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Duration of Hospitalization
Time between admission to the hospital and discharge from the hospital
Total Parenteral Opioid Usage
Sum of all parenteral opioids used during the study period in milligrams (mg) of morphine or morphine equivalents.
Occurrence of Azotemia
Participants who had measured values of blood urea nitrogen (BUN), serum creatinine, or both that were above the upper limit of normal for age.
Fluid Retention
Number of participants who had clinically overt fluid retention as determined by history, physical examination, vital signs, and weight (e.g., peripheral edema, increase in weight)
Hematuria
Number of participants who had microscopic hematuria as determined by urinalysis
Dyspepsia
Number of participants who reported discomfort in the stomach related to eating or drinking
Gastrointestinal Ulceration
Number of participants who had gastrointestinal ulceration.
Bleeding
Number of participants who had clinically overt bleeding from any site. This excludes microscopic hematuria only.

Full Information

First Posted
June 21, 2005
Last Updated
October 6, 2020
Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), University of Texas Southwestern Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT00115336
Brief Title
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

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Terminated
Why Stopped
Poor accrual
Study Start Date
January 2005 (undefined)
Primary Completion Date
August 2008 (Actual)
Study Completion Date
December 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), University of Texas Southwestern Medical Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Diseases, Anemia, Sickle Cell
Keywords
Blood Diseases, Sickle Cell Anemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1-Intravenous ketorolac and oral placebo
Arm Type
Active Comparator
Arm Description
Intravenous ketorolac and oral placebo
Arm Title
2-Intravenous placebo and oral ibuprofen
Arm Type
Active Comparator
Arm Description
Intravenous placebo and oral ibuprofen
Intervention Type
Drug
Intervention Name(s)
Intravenous Ketorolac
Other Intervention Name(s)
Toradol
Intervention Description
Intravenous ketorolac
Intervention Type
Drug
Intervention Name(s)
Ibuprofen
Other Intervention Name(s)
Motrin, Advil
Intervention Description
Ibuprofen, taken orally
Primary Outcome Measure Information:
Title
Time to a 50% Reduction in Reported Pain Intensity
Description
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
Time Frame
Measured every 4 hours during hospitalization, over a mean hospitalization duration of 81.5 hours.
Secondary Outcome Measure Information:
Title
Duration of Hospitalization
Description
Time between admission to the hospital and discharge from the hospital
Time Frame
The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.
Title
Total Parenteral Opioid Usage
Description
Sum of all parenteral opioids used during the study period in milligrams (mg) of morphine or morphine equivalents.
Time Frame
The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.
Title
Occurrence of Azotemia
Description
Participants who had measured values of blood urea nitrogen (BUN), serum creatinine, or both that were above the upper limit of normal for age.
Time Frame
The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.
Title
Fluid Retention
Description
Number of participants who had clinically overt fluid retention as determined by history, physical examination, vital signs, and weight (e.g., peripheral edema, increase in weight)
Time Frame
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)
Title
Hematuria
Description
Number of participants who had microscopic hematuria as determined by urinalysis
Time Frame
The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.
Title
Dyspepsia
Description
Number of participants who reported discomfort in the stomach related to eating or drinking
Time Frame
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)
Title
Gastrointestinal Ulceration
Description
Number of participants who had gastrointestinal ulceration.
Time Frame
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)
Title
Bleeding
Description
Number of participants who had clinically overt bleeding from any site. This excludes microscopic hematuria only.
Time Frame
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charles T. Quinn, MD
Organizational Affiliation
University of Texas Southwestern Medical Center
Official's Role
Study Chair
Facility Information:
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Ketorolac Versus Ibuprofen to Treat Painful Episodes of Sickle Cell Disease

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