Hematologic DiseasesPhase 4NCT00115336
Ketorolac Versus Ibuprofen to Treat Painful Episodes of Sickle Cell Disease
A Phase 4 study testing Intravenous Ketorolac and Ibuprofen in people with Hematologic Diseases and Anemia, Sickle Cell, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 6 to 18 years
- Conditions the study is for
- Hematologic Diseases, Anemia, Sickle Cell
- What is being tested?
- Intravenous Ketorolac and Ibuprofen
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2005to Dec 2008
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
About this study
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).
Read the 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.
- Conditions
- Hematologic Diseases, Anemia, Sickle Cell
- Being tested
- Intravenous Ketorolac, Ibuprofen
- Keywords
- Blood Diseases, Sickle Cell Anemia
- Medical subject headings
- Hematologic Diseases, Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous KetorolacDrug
Also called Toradol
Intravenous ketorolac
IbuprofenDrug
Also called Motrin, Advil
Ibuprofen, taken orally
| Study group | Role | What they receive |
|---|---|---|
| 1-Intravenous ketorolac and oral placebo | Active comparator | Intravenous ketorolac and oral placebo Receives: Drug: Intravenous Ketorolac |
| 2-Intravenous placebo and oral ibuprofen | Active comparator | Intravenous placebo and oral ibuprofen Receives: Drug: Ibuprofen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: Measured every 4 hours during hospitalization, over a mean hospitalization duration of 81.5 hours.
Secondary outcomes (8)
Duration of Hospitalization
Time between admission to the hospital and discharge from the hospital
Measured: The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.
Total Parenteral Opioid Usage
Sum of all parenteral opioids used during the study period in milligrams (mg) of morphine or morphine equivalents.
Measured: The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.
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.
Measured: The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.
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)
Measured: 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
Number of participants who had microscopic hematuria as determined by urinalysis
Measured: The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.
Dyspepsia
Number of participants who reported discomfort in the stomach related to eating or drinking
Measured: 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)
Gastrointestinal Ulceration
Number of participants who had gastrointestinal ulceration.
Measured: 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)
Bleeding
Number of participants who had clinically overt bleeding from any site. This excludes microscopic hematuria only.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2005 (estimated)
- Study startJan 2005
- Primary completionAug 2008
- Study completionDec 2008
Why it stopped: Poor accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hematologic DiseasesStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), University of Texas Southwestern Medical Center
- Responsible party
- Sponsor
- Investigators
- Charles T. Quinn, MD, Study chair, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00115336
- Sponsor's protocol ID
- 191
- Other IDs
- U54HL070588
- Status last verified
- Sep 2020
- First submitted
- 21 Jun 2005
- Last updated
- 8 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketorolac Versus Ibuprofen for the Painful Crisis of Sickle Cell Disease - Southwestern Comprehensive Sickle Cell Center
- ClinicalTrials.gov ID
- NCT00115336
- Acronym / sponsor ID
- 191
- Conditions
- Hematologic Diseases, Anemia, Sickle Cell
- Keywords
- Blood Diseases, Sickle Cell Anemia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor accrual
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), University of Texas Southwestern Medical Center
- Study start
- Jan 2005
- Primary completion
- Aug 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 22 Jun 2005 (estimated)
- Results
- Posted 8 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1-Intravenous ketorolac and oral placebo | Active comparator | Drug: Intravenous KetorolacIntravenous ketorolac and oral placebo |
| 2-Intravenous placebo and oral ibuprofen | Active comparator | Drug: IbuprofenIntravenous placebo and oral ibuprofen |
Who may qualify
- Ages
- 6 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (17 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous KetorolacAlso: ToradolIntravenous ketorolac | Drug | 1-Intravenous ketorolac and oral placebo |
| IbuprofenAlso: Motrin, AdvilIbuprofen, taken orally | Drug | 2-Intravenous placebo and oral ibuprofen |
Primary outcome
Time to a 50% Reduction in Reported Pain Intensity
Time frame: Measured every 4 hours during hospitalization, over a mean hospitalization duration of 81.5 hours.
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
8 secondary outcomes
Duration of Hospitalization
Time frame: The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.
Total Parenteral Opioid Usage
Time frame: The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.
Occurrence of Azotemia
Time frame: The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.
Fluid Retention
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)
Hematuria
Time frame: The duration of the entire hospitalization, over a mean hospitalization duration of 81.5 hours.
Dyspepsia
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)
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)
Bleeding
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles T. Quinn, MD study chair
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Intravenous Ketorolac and Ibuprofen in people with Hematologic Diseases and Anemia, Sickle Cell, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to a 50% Reduction in Reported Pain Intensity (time frame: Measured every 4 hours during hospitalization, over a mean hospitalization duration of 81.5 hours.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2020.