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

Trial Summary

What is the purpose of this trial?

Sickle cell disease (SCD) is an inherited blood disorder affecting approximately 36,000 children in the United States, approximately 90% of whom are Black. The disease is characterized by recurrent, severe pain crises which result in high rates of emergency department visits and hospitalizations, and decreased quality of life. The National Heart, Lung and Blood Institute, as well as the American Society of Hematology, have endorsed pain management guidelines regarding the timeliness of care for children presenting with these acute pain crises. These evidence-based guidelines are infrequently followed, resulting in increased pain and hospitalizations. In additional to other barriers to following the guideline, structural racism has been proposed as a significant contributor and the New England Journal of Medicine recently called for the institution of SCD-specific pain management protocols to combat structural racism and reduce time to opioid administration. The investigators' long-term goal is to improve the care and health outcomes of children with acute painful vaso-occlusive crisis treated in the emergency department. The overall aim of the investigators is to test a care pathway using multifaceted implementation strategies to increase guideline adherent care for children in the emergency department with acute painful vaso-occlusive crisis.

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 data supports the effectiveness of the drug Crizanlizumab-tmca for treating sickle cell crisis?

Research shows that Crizanlizumab, a drug that helps prevent sickle-shaped red blood cells from sticking together, can reduce the number of painful episodes in people with sickle cell disease. It has been shown to lower the rate of these crises and improve quality of life, although some patients may experience infusion-related reactions. ^{1 2 3 4 5}

Is crizanlizumab (Adakveo) safe for humans?

Crizanlizumab has been shown to have a favorable safety profile in clinical trials for sickle cell disease, with some patients experiencing infusion-related reactions, joint pain, diarrhea, and nausea. Serious side effects were similar to those seen with a placebo, but long-term safety data is still limited. ^{4 5 6 7 8}

How is the drug crizanlizumab unique in treating sickle cell disease?

Crizanlizumab is unique because it is the first monoclonal antibody (a type of protein made in the lab to fight infections) approved to reduce the frequency of painful vaso-occlusive crises in sickle cell disease. It works by blocking P-selectin, a molecule that contributes to these crises, and is given as a monthly intravenous infusion. ^{3 6 7 8 9}

Research Team

David Brousseau, MD, MS

Principal Investigator

Nemours Children's Health

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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, 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]

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]

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 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, 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Hospitalist management of vaso-occlusive pain crisis in patients with sickle cell disease using a pathway of care. [2014]

2. United States 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Crizanlizumab and comparators for adults with sickle cell disease: a systematic review and network meta-analysis. [2021]

4. New Zealand pubmed.ncbi.nlm.nih.gov

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

5. Switzerland 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Crizanlizumab for the Prevention of Vaso-Occlusive Pain Crises in Sickle Cell Disease. [2022]

7. United States 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. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Crizanlizumab: First Approval. [2020]

9. United States 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. [2021]