Sickle Cell DiseasePhase 4NCT06579703
Ketorolac for Acute Vaso-Occlusive Crisis in Pediatric Sickle Cell Disease
A Phase 4 study testing Ketorolac in people with Sickle Cell Disease and Sickle Cell Crisis, run by Children's Blood and Cancer Center at Dell Children's Medical Center.
Trial summary
Pediatric patients who present with acute vaso-occlusive pain crisis may have equivalent pain reduction scores at lower dosing of intravenous Ketorolac compared to standard dosing of 0.5 mg/kg/dose IV (<16yo max 15mg, >16yo max 30mg) x 1 dose. Read more about this study
- Who is it for?
- Ages 1 day to 21 years
- Conditions the study is for
- Sickle Cell Disease, Sickle Cell Crisis, Veno-occlusive Disease
- What is being tested?
- Ketorolac
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- No sites listed yet
- Study dates
- 30 Sep 2024to 15 Feb 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 1 day to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Pediatric patients with sickle cell disease (any genotype) who present to DCMC Emergency department or outpatient hematology clinic with acute pain.
Who cannot join
- Patients receiving NSAID medication <6 hours from presentation
- known kidney injury
- sickle nephropathy
- bleeding concerns
- allergy to NSAID medication
- chronic pain patient
- hemodynamic instability as defined by the treating provider
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Ketorolac Dosing for Acute Vaso-Occlusive Crisis in Pediatric Patients With Sickle Cell Disease
Pediatric patients who present with acute vaso-occlusive pain crisis may have equivalent pain reduction scores at lower dosing of intravenous Ketorolac compared to standard dosing of 0.5 mg/kg/dose IV (<16yo max 15mg, >16yo max 30mg) x 1 dose.
Read the detailed description
Sickle Cell Disease is characterized by a point mutation that causes red cell polymerization and clinically results in pain events, called vaso-occlusive crises (VOC), and end organ damage. VOC is the most common reason for hospital admissions and ER visits in the SCD population. Ketorolac is an NSAID class medication widely used for pain. Ketorolac reversibly inhibits cyclooxygenase-1 and cyclooxygenase-2 and inhibits the formation of prostaglandins and thromboxane. Specifically, in the SCD pediatric population, Ketorolac was shown to provide adequate pain relief without the need for additional IV analgesics in 50% of patients presenting to the emergency department with VOC. Despite its potential benefits, adverse effects from Ketorolac at standard dosing include gastrointestinal hemorrhage, nephrotoxicity and drug-drug interactions, some of which are dose-dependent. Patients with SCD may be particularly vulnerable to acute kidney injury from nephrotoxic medications given the propensity for chronic kidney disease from ongoing anemia, hemolysis and inflammation. A retrospective review in hospitalized patients with SCD who received at least one dose of ketorolac found that higher doses of ketorolac was a risk factor for acute kidney injury. In addition, a case report on a pediatric patient with SCD showed irreversible renal failure and bleeding complications after administration of ketorolac, despite adequate hydration. The American Society of Hematology guidelines for management of acute and chronic pain in patients with sickle cell disease recommend a short course of NSAIDs in addition to opioids for acute pain management based on very low certainty of evidence.
Several adult studies have suggested that the efficacy of ketorolac analgesia at 10mg is equivalent to higher doses (15mg-90mg) for treatment of various pain syndromes in the ED setting, post-operative and cancer pain. However, these studies excluded patients with SCD whose pain mechanism and pain thresholds may differ from these populations.
The investigators propose a prospective, randomized, double blind clinical trial that will take place in the DCMC Emergency Department and Children's Blood and Cancer Center Hematology Outpatient clinic.
- Being tested
- Ketorolac
- Medical subject headings
- Anemia, Sickle Cell, Vaso-Occlusive Crises
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetorolacDrug
Also called Toradol
Randomized to a single dose of:
Arm A: 15 mg/mL (per mL) Arm B: 30 mg/mL (per mL)
| Study group | Role | What they receive |
|---|---|---|
| Reduced dose Ketorolac Arm A | Experimental | a reduced dose of Ketorolac, 15 mg/mL Receives: Drug: Ketorolac |
| Standard of care dose Ketorolac Arm B | Active comparator | standard of care dose of Ketorolac, 30mg/mL Receives: Drug: Ketorolac |
What is being measured
The primary outcome is the main question the study is designed to answer.
FACES Pain Scale-Revised(FPS-R)
Has a range from 0 to 10 possible. 0 to 3 mild pain, 4 to 6 moderate pain, 7 to 10 severe pain.
Measured: Assessed before dose of pain medication and 30 minutes post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2024
- Study start30 Sep 2024 (estimated)
- Primary completion1 Jul 2027 (estimated)
- Study completion15 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- 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
- Model description
- Randomized to 1 of 2 arms, parallel dosing
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 102 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Blood and Cancer Center at Dell Children's Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alicia Chang, MD, Principal investigator, Director, Comprehensive Sickle Cell Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06579703
- Sponsor's protocol ID
- Chang_pain in SCD
- Status last verified
- Aug 2024
- First submitted
- 24 Jul 2024
- Last updated
- 30 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Brandow AM, Carroll CP, Creary S, Edwards-Elliott R, Glassberg J, Hurley RW, Kutlar A, Seisa M, Stinson J, Strouse JJ, Yusuf F, Zempsky W, Lang E. American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain. Blood Adv. 2020 Jun 23;4(12):2656-2701. doi: 10.1182/bloodadvances.2020001851.
PubMed 32559294Shapiro BS. The management of pain in sickle cell disease. Pediatr Clin North Am. 1989 Aug;36(4):1029-45. doi: 10.1016/s0031-3955(16)36735-9.
PubMed 2666928Jones SF, O'Donnell AM. Clinical pharmacology: traditional NSAIDs and Jones SF, O'Donnell AM. Clinical pharmacology: traditional NSAIDs and selective COX-2 inhibitors. In: Macintyre PE, Walker SM, Rowbotham DJ, et al, eds. Clinical Pain Management (Acute Pain). 2nd ed. London, England: Hodder & Stoughton Limited; 2008:79.
Motov S, Yasavolian M, Likourezos A, Pushkar I, Hossain R, Drapkin J, Cohen V, Filk N, Smith A, Huang F, Rockoff B, Homel P, Fromm C. Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med. 2017 Aug;70(2):177-184. doi: 10.1016/j.annemergmed.2016.10.014. Epub 2016 Dec 16.
PubMed 27993418Staquet MJ. A double-blind study with placebo control of intramuscular ketorolac tromethamine in the treatment of cancer pain. J Clin Pharmacol. 1989 Nov;29(11):1031-6. doi: 10.1002/j.1552-4604.1989.tb03274.x.
PubMed 2689472Minotti V, Betti M, Ciccarese G, Fumi G, Tonato M, Del Favero A. A double-blind study comparing two single-dose regimens of ketorolac with diclofenac in pain due to cancer. Pharmacotherapy. 1998 May-Jun;18(3):504-8.
PubMed 9620101Brown CR, Moodie JE, Wild VM, Bynum LJ. Comparison of intravenous ketorolac tromethamine and morphine sulfate in the treatment of postoperative pain. Pharmacotherapy. 1990;10(6 ( Pt 2)):116S-121S.
PubMed 2082307Simckes AM, Chen SS, Osorio AV, Garola RE, Woods GM. Ketorolac-induced irreversible renal failure in sickle cell disease: a case report. Pediatr Nephrol. 1999 Jan;13(1):63-7. doi: 10.1007/s004670050565.
PubMed 10100293Baddam S, Aban I, Hilliard L, Howard T, Askenazi D, Lebensburger JD. Acute kidney injury during a pediatric sickle cell vaso-occlusive pain crisis. Pediatr Nephrol. 2017 Aug;32(8):1451-1456. doi: 10.1007/s00467-017-3623-6. Epub 2017 Feb 25.
PubMed 28238158
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketorolac Dosing for Acute Vaso-Occlusive Crisis in Pediatric Patients With Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT06579703
- Acronym / sponsor ID
- Chang_pain in SCD
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 102 participants (estimated)
- Lead sponsor
- Children's Blood and Cancer Center at Dell Children's Medical CenterUniversity, hospital or other
- Study start
- 30 Sep 2024 (estimated)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 15 Feb 2028 (estimated)
- First posted
- 30 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pediatric patients who present with acute vaso-occlusive pain crisis may have equivalent pain reduction scores at lower dosing of intravenous Ketorolac compared to standard dosing of 0.5 mg/kg/dose IV (<16yo max 15mg, >16yo max 30mg) x 1 dose.
Detailed description
Sickle Cell Disease is characterized by a point mutation that causes red cell polymerization and clinically results in pain events, called vaso-occlusive crises (VOC), and end organ damage. VOC is the most common reason for hospital admissions and ER visits in the SCD population. Ketorolac is an NSAID class medication widely used for pain. Ketorolac reversibly inhibits cyclooxygenase-1 and cyclooxygenase-2 and inhibits the formation of prostaglandins and thromboxane. Specifically, in the SCD pediatric population, Ketorolac was shown to provide adequate pain relief without the need for additional IV analgesics in 50% of patients presenting to the emergency department with VOC. Despite its potential benefits, adverse effects from Ketorolac at standard dosing include gastrointestinal hemorrhage, nephrotoxicity and drug-drug interactions, some of which are dose-dependent. Patients with SCD may be particularly vulnerable to acute kidney injury from nephrotoxic medications given the propensity for chronic kidney disease from ongoing anemia, hemolysis and inflammation. A retrospective review in hospitalized patients with SCD who received at least one dose of ketorolac found that higher doses of ketorolac was a risk factor for acute kidney injury. In addition, a case report on a pediatric patient with SCD showed irreversible renal failure and bleeding complications after administration of ketorolac, despite adequate hydration. The American Society of Hematology guidelines for management of acute and chronic pain in patients with sickle cell disease recommend a short course of NSAIDs in addition to opioids for acute pain management based on very low certainty of evidence.
Several adult studies have suggested that the efficacy of ketorolac analgesia at 10mg is equivalent to higher doses (15mg-90mg) for treatment of various pain syndromes in the ED setting, post-operative and cancer pain. However, these studies excluded patients with SCD whose pain mechanism and pain thresholds may differ from these populations.
The investigators propose a prospective, randomized, double blind clinical trial that will take place in the DCMC Emergency Department and Children's Blood and Cancer Center Hematology Outpatient clinic.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized to 1 of 2 arms, parallel dosing
| Arm | Type | Receives |
|---|---|---|
| Reduced dose Ketorolac Arm A | Experimental | Drug: Ketorolaca reduced dose of Ketorolac, 15 mg/mL |
| Standard of care dose Ketorolac Arm B | Active comparator | Drug: Ketorolacstandard of care dose of Ketorolac, 30mg/mL |
Who may qualify
- Ages
- 1 day to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (1 listed)
- Pediatric patients with sickle cell disease (any genotype) who present to DCMC Emergency department or outpatient hematology clinic with acute pain.
Key exclusion criteria (7 listed)
- Patients receiving NSAID medication <6 hours from presentation
- known kidney injury
- sickle nephropathy
- bleeding concerns
- allergy to NSAID medication
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 |
|---|---|---|
| KetorolacAlso: ToradolRandomized to a single dose of: Arm A: 15 mg/mL (per mL) Arm B: 30 mg/mL (per mL) | Drug | Reduced dose Ketorolac Arm A, Standard of care dose Ketorolac Arm B |
Primary outcome
FACES Pain Scale-Revised(FPS-R)
Time frame: Assessed before dose of pain medication and 30 minutes post-dose
Has a range from 0 to 10 possible. 0 to 3 mild pain, 4 to 6 moderate pain, 7 to 10 severe pain.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2024.
- Background: PubMed 32559294Brandow AM, Carroll CP, Creary S, Edwards-Elliott R, Glassberg J, Hurley RW, Kutlar A, Seisa M, Stinson J, Strouse JJ, Yusuf F, Zempsky W, Lang E. American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain. Blood Adv. 2020 Jun 23;4(12):2656-2701. doi: 10.1182/bloodadvances.2020001851.
- Results publication: PubMed 2666928Shapiro BS. The management of pain in sickle cell disease. Pediatr Clin North Am. 1989 Aug;36(4):1029-45. doi: 10.1016/s0031-3955(16)36735-9.
- Results publicationJones SF, O'Donnell AM. Clinical pharmacology: traditional NSAIDs and Jones SF, O'Donnell AM. Clinical pharmacology: traditional NSAIDs and selective COX-2 inhibitors. In: Macintyre PE, Walker SM, Rowbotham DJ, et al, eds. Clinical Pain Management (Acute Pain). 2nd ed. London, England: Hodder & Stoughton Limited; 2008:79.
- Results publication: PubMed 27993418Motov S, Yasavolian M, Likourezos A, Pushkar I, Hossain R, Drapkin J, Cohen V, Filk N, Smith A, Huang F, Rockoff B, Homel P, Fromm C. Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med. 2017 Aug;70(2):177-184. doi: 10.1016/j.annemergmed.2016.10.014. Epub 2016 Dec 16.
- Results publication: PubMed 2689472Staquet MJ. A double-blind study with placebo control of intramuscular ketorolac tromethamine in the treatment of cancer pain. J Clin Pharmacol. 1989 Nov;29(11):1031-6. doi: 10.1002/j.1552-4604.1989.tb03274.x.
- Results publication: PubMed 9620101Minotti V, Betti M, Ciccarese G, Fumi G, Tonato M, Del Favero A. A double-blind study comparing two single-dose regimens of ketorolac with diclofenac in pain due to cancer. Pharmacotherapy. 1998 May-Jun;18(3):504-8.
- Results publication: PubMed 2082307Brown CR, Moodie JE, Wild VM, Bynum LJ. Comparison of intravenous ketorolac tromethamine and morphine sulfate in the treatment of postoperative pain. Pharmacotherapy. 1990;10(6 ( Pt 2)):116S-121S.
- Results publication: PubMed 10100293Simckes AM, Chen SS, Osorio AV, Garola RE, Woods GM. Ketorolac-induced irreversible renal failure in sickle cell disease: a case report. Pediatr Nephrol. 1999 Jan;13(1):63-7. doi: 10.1007/s004670050565.
- Results publication: PubMed 28238158Baddam S, Aban I, Hilliard L, Howard T, Askenazi D, Lebensburger JD. Acute kidney injury during a pediatric sickle cell vaso-occlusive pain crisis. Pediatr Nephrol. 2017 Aug;32(8):1451-1456. doi: 10.1007/s00467-017-3623-6. Epub 2017 Feb 25.
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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.
Alicia Chang, MD principal investigator
Director, Comprehensive Sickle Cell Center
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ketorolac in people with Sickle Cell Disease and Sickle Cell Crisis, run by Children's Blood and Cancer Center at Dell Children's Medical Center.
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 1 inclusion and 7 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: opening soon, as of the sponsor's last update on 30 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rhea Robinson, RN, BSN (512-628-1902, Rmrobinson@ascension.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
FACES Pain Scale-Revised(FPS-R) (time frame: Assessed before dose of pain medication and 30 minutes post-dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06579703, which also lists 9 linked publications.
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 30 Aug 2024.