Enhanced Emergency Care for Sickle Cell Crisis

(SCIENCE Trial)

Overseen By David Brousseau, MD, MS

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Medical College of Wisconsin

Disqualifiers: Acute chest syndrome, Fever, Priapism, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

5328 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to enhance emergency care for children with sickle cell disease experiencing severe pain episodes. Researchers will test a new care pathway, which includes Adakveo (Crizanlizumab-tmca), an intravenous drug, to ensure timely pain management in the emergency department according to established guidelines. The trial involves two groups: one receiving the new care approach immediately and another receiving it later. It seeks children with sickle cell disease who visit the emergency department for pain crises and have received at least one opioid for pain relief. As an unphased trial, this study offers a unique opportunity to improve emergency care for children with sickle cell disease.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this care pathway is safe for children with sickle cell crisis?

Research has shown that treatments for sickle cell disease, such as crizanlizumab (Adakveo), have undergone safety testing in other studies. These studies found that patients using crizanlizumab experienced fewer pain crises, which are severe pain episodes caused by the disease. This suggests the treatment is generally safe, although some patients might experience side effects like protein or blood in their urine, as noted in safety reviews.

Although this trial focuses on a care pathway rather than a specific drug, it is reassuring to know that treatments for sickle cell crises have a strong safety record. This provides confidence in the overall safety of methods used to manage sickle cell pain crises. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Enhanced Emergency Care for Sickle Cell Crisis trial because it aims to optimize the care pathway for patients experiencing a sickle cell crisis. Unlike current treatments that primarily focus on pain management and hydration, this approach seeks to streamline emergency care procedures, potentially reducing wait times and improving overall patient outcomes. By implementing a structured care pathway, the goal is to provide faster, more efficient care tailored to the unique needs of sickle cell patients. This could lead to quicker pain relief and a reduction in complications associated with prolonged crisis episodes.

What evidence suggests that this care pathway is effective for sickle cell crisis?

Research has shown that specific care plans can improve the management of sickle cell crises in the emergency room. These plans aim to provide faster and more effective pain relief by following expert guidelines. This trial will evaluate the effectiveness of different care pathways for managing sickle cell crises. Although crizanlizumab is not part of this trial, studies have found that timely treatments like it can greatly reduce the number of painful episodes for sickle cell patients. Specifically, crizanlizumab has significantly decreased these pain crises, supporting the idea that focused care plans are beneficial. By closely following care guidelines, children with sickle cell disease may experience less pain and fewer hospital visits. This approach seeks to offer better and fairer care, addressing issues like unequal treatment in healthcare. ^{1 2 4 5 6}

Who Is on the Research Team?

David Brousseau, MD, MS

Principal Investigator

Nemours Children's Health

Are You a Good Fit for This Trial?

This trial is for children with Sickle Cell Disease (SCD) who visit the emergency department due to a pain crisis and have received at least one opioid. It's not for those with fever over 38.5°C, priapism, sickle cell trait, or acute chest syndrome during their ED visit.

Inclusion Criteria

I have been diagnosed with sickle cell disease.

I have taken opioids at least once.

I visited the ER for a pain crisis that didn't have complications.

Exclusion Criteria

Fever > 38.5 in the ED

I have experienced prolonged erections.

I have sickle cell trait.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Intervention

Implementation of a care pathway using multifaceted strategies to increase guideline adherent care for children with acute painful vaso-occlusive crisis in the emergency department

6 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after intervention

2-4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Care pathway

Trial Overview The study tests a care pathway designed to ensure that children with SCD receive timely and guideline-adherent pain management in the emergency department. The goal is to reduce hospitalizations and improve quality of life by adhering to established pain management guidelines.

How Is the Trial Designed?

Group I: Post-intervention Active Control 1 Intervention

Group II: Delayed intervention Active Control 1 Intervention

Care pathway is already approved in United States, European Union for the following indications:

Approved in United States as Adakveo for:

• Sickle Cell Disease

Approved in European Union as Adakveo for:

• Sickle Cell Disease

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Nemours Children's Health System

Collaborator

Trials

11

Recruited

17,400+

Pediatric Emergency Care Applied Research Network

Collaborator

Trials

6

Recruited

13,400+

Published Research Related to This Trial

The implementation of a care pathway for patients with sickle cell disease experiencing vaso-occlusive pain crises led to a significant reduction in average hospital length of stay by 1.44 days, indicating improved efficiency in care.

The pathway emphasized early use of patient-controlled analgesia (PCA) for pain management, which increased PCA usage, although other patient outcomes such as readmission rates and transfusion needs did not show significant changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hospitalist management of vaso-occlusive pain crisis in patients with sickle cell disease using a pathway of care. Allen Liles, E., Kirsch, J., Gilchrist, M., et al.[2014]

Crizanlizumab, a monoclonal antibody targeting P-selectin, received conditional marketing authorization in the EU for preventing recurrent vaso-occlusive crises in sickle cell disease patients aged 16 and older, showing a 45.3% reduction in annual pain crises at a high dose compared to placebo.

The treatment was found to have a similar safety profile to placebo, with common side effects including infusion-related reactions and arthralgia, indicating that crizanlizumab is both effective and relatively safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Crizanlizumab for the Prevention of Recurrent Vaso-Occlusive Crises in Patients With Sickle Cell Disease. Delgado, J., Voltz, C., Stain, M., et al.[2021]

Crizanlizumab, a P-selectin inhibitor approved in 2019, significantly reduces the frequency of vaso-occlusive crises (VOCs) in sickle cell disease (SCD) patients, with a 45% decrease in VOC incidence observed in the SUSTAIN trial involving multiple centers.

The safety profile of crizanlizumab is comparable to that of a placebo, making it a promising new treatment option for SCD, with ongoing studies exploring its effects in pediatric patients and on other complications related to the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of Crizanlizumab: A New Parenteral Option to Reduce Vaso-occlusive Pain Crises in Patients with Sickle Cell Disease. Han, J., Saraf, SL., Gordeuk, VR.[2021]

Crizanlizumab, a new treatment for sickle cell disease (SCD), has shown promise in reducing the annual rates of vaso-occlusive crises (VOC) with a favorable safety profile, marking a significant advancement in therapy options beyond hydroxyurea.

While hydroxyurea has been effective in decreasing VOC and hospitalizations, adherence to this treatment can be challenging due to side effects; crizanlizumab offers a new approach that may improve patient compliance and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of crizanlizumab and its potential in the prevention of pain crises in sickle cell disease: evidence to date. Riley, TR., Riley, TT.[2020]

Crizanlizumab is the first monoclonal antibody approved for sickle cell disease, specifically designed to reduce the frequency of vaso-occlusive pain crises, based on data from a phase 2 clinical trial.

This medication is administered as a monthly intravenous infusion for patients aged 16 and older, showing efficacy in crisis prevention, although concerns about cost and long-term safety remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizanlizumab for the Prevention of Vaso-Occlusive Pain Crises in Sickle Cell Disease. Stevens, DL., Hix, M., Gildon, BL.[2022]

Implementing a clinical pathway in the pediatric emergency department significantly reduced the time to administer the first analgesic for sickle cell vaso-occlusive crisis pain from 74 minutes to 42 minutes, improving patient care.

The percentage of patients receiving ketorolac increased from 57% to 82% after the pathway was introduced, indicating enhanced adherence to pain management protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of a clinical pathway to improve the acute management of vaso-occlusive crisis pain in pediatric sickle cell disease. Ender, KL., Krajewski, JA., Babineau, J., et al.[2022]

Crizanlizumab is a monoclonal antibody that effectively reduces the frequency of vaso-occlusive crises (VOCs) in patients with sickle cell disease by blocking P-selectin, which is crucial for cell adhesion and inflammation.

Approved in the USA in November 2019 for adults and pediatric patients aged 16 and older, crizanlizumab is also under review in the EU and being studied for use in myelofibrosis, indicating its potential versatility in treating blood-related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizanlizumab: First Approval. Blair, HA.[2020]

Crizanlizumab significantly reduces the frequency of vaso-occlusive crises (VOC) in patients with sickle cell disease, showing a hazard ratio of 0.55 compared to placebo, based on a network meta-analysis of 9 randomized controlled trials.

The treatment also decreases all-cause hospitalisation days without increasing the risk of adverse events, indicating it is both effective and safe for older adolescents and adults with sickle cell disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizanlizumab and comparators for adults with sickle cell disease: a systematic review and network meta-analysis. Thom, H., Jansen, J., Shafrin, J., et al.[2021]

Crizanlizumab, a monoclonal antibody approved for treating sickle cell-related pain crises, showed significant benefits in a 19-year-old patient, including preventing acute chest syndrome and improving quality of life, despite experiencing a severe infusion-related reaction during treatment.

The case highlights that, even after a painful infusion reaction, continued treatment with crizanlizumab can lead to positive outcomes, suggesting that patients may benefit from persisting with the therapy under medical guidance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short- and long-term follow-up and additional benefits in a sickle cell disease patient experienced severe crizanlizumab infusion-related vaso-occlusive crisis: A case report. Alshurafa, A., Yassin, MA.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8255978/

Crizanlizumab for the Prevention of Vaso-Occlusive Pain ... Abstract. Objective: To review the efficacy and safety of crizanlizumab (Adakveo) in the prevention of vaso-occlusive pain crises in sickle cell disease.

2. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2019/761128Orig1s000MultidisciplineR.pdf

761128Orig1s000 - accessdata.fda.gov There is substantial evidence for the conclusion of effectiveness for ADAKVEO in patients with sickle cell disease. 8.2 Review of Safety. 8.2 ...

3. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/64/NCT04053764/Prot_000.pdf

SEG101/Crizanlizumab Outcome of sickle cell anemia: a 4-decade observational study of 1056 patients. Medicine (Baltimore); 84(6):363-76. Saraf SL, Viner M ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34752581/

Crizanlizumab for the Prevention of Vaso-Occlusive Pain ... Conclusion: Crizanlizumab appears to be an efficacious therapy for patients with sickle cell disease to reduce the frequency of vaso-occlusive crises. Concerns ...

5. novartis.com novartis.com/us-en/news/media-releases/new-novartis-medicine-adakveo-crizanlizumab-tmca-approved-fda-reduce-frequency-pain-crises-individuals-living-sickle-cell-disease

New Novartis medicine Adakveo® (crizanlizumab-tmca ... "We know this drug can decrease the frequency of sickle cell pain crises in a significant and clinically meaningful way," said Kenneth Ataga, MD ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01895361

NCT01895361 | Study to Assess Safety and Impact of ... The purpose of this study was to determine whether the investigational drug SelG1 when given to sickle cell disease patients either taking or not taking ...