Enhanced Emergency Care for Sickle Cell Crisis
(SCIENCE Trial)
Recruiting in Palo Alto (17 mi)
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Medical College of Wisconsin
Disqualifiers: Acute chest syndrome, Fever, Priapism, others
No Placebo Group
Approved in 2 Jurisdictions
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.
12345Is 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.
45678How 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.
36789Eligibility 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.
+1 more
Trial 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
Participant Groups
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.
2Treatment groups
Active Control
Group I: Post-interventionActive Control1 Intervention
Group II: Delayed interventionActive Control1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Children's WisconsinMilwaukee, WI
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Who Is Running the Clinical Trial?
Medical College of WisconsinLead Sponsor
Nemours Children's Health SystemCollaborator
Pediatric Emergency Care Applied Research NetworkCollaborator
References
Hospitalist management of vaso-occlusive pain crisis in patients with sickle cell disease using a pathway of care. [2014]Patients with sickle cell disease (SCD) suffer from intermittent vaso-occlusive pain crises (VOCs). These crises lead to frequent hospitalizations, significant morbidity, and increased mortality risk. Care pathways can enhance efficiency and quality of care. Our study sought to evaluate the development and implementation of a care pathway for patients with SCD experiencing VOCs.
Use of a clinical pathway to improve the acute management of vaso-occlusive crisis pain in pediatric sickle cell disease. [2022]The most common, debilitating morbidity of sickle cell disease (SCD) is vaso-occlusive crisis (VOC) pain. Although guidelines exist for its management, they are generally not well-followed, and research in other pediatric diseases has shown that clinical pathways improve care. The purpose of our study was to determine whether a clinical pathway improves the acute management of sickle cell vaso-occlusive crisis (VOC) pain in the pediatric emergency department (PED).
Crizanlizumab and comparators for adults with sickle cell disease: a systematic review and network meta-analysis. [2021]Treatment options for preventing vaso-occlusive crises (VOC) among patients with sickle cell disease (SCD) are limited, especially if hydroxyurea treatment has failed or is contraindicated. A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the efficacy and safety of crizanlizumab for older adolescent and adult (≥16 years old) SCD patients.
Profile of crizanlizumab and its potential in the prevention of pain crises in sickle cell disease: evidence to date. [2020]Sickle cell disease (SCD) is one of the most common inherited blood disorders globally. It is a grouping of autosomal recessive genetic disorders identified by a genetic mutation that replaces glutamic acid with valine at the sixth amino acid on the hemoglobin β-globin chain. Millions of people around the world live with a severe genotype of SCD that is often associated with occlusion of the microvasculature resulting in episodes of severe pain and multiple organ system dysfunction. These episodes, commonly categorized as vaso-occlusive crises (VOC), are a distinctive clinical presentation of SCD which represents the majority of SCD morbidity and associated hospitalizations. Though the complete process by which these crises occur is complex and not fully outlined, evidence reveals this process to be multifactorial and heterocellular. For nearly two decades, hydroxyurea was the only FDA-approved therapy for SCD. Evidence to date shows that hydroxyurea treatment significantly reduces the rate of VOC, hospitalizations, and mortality. Despite these benefits, adherence remains problematic due to a variety of adverse effects and interpatient variability connected with hydroxyurea therapy. Crizanlizumab, an adhesion inhibitor of sickled red blood cells, was recently granted breakthrough therapy designation. Results of a phase 2 study have reported a successful reduction in annual rates of vaso-occlusive crisis with a favorable safety profile. This paper reviews the available literature concerning crizanlizumab use in patients with SCD.
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]Sickle cell disease is an autosomal recessive disorder characterized by the presence of sickle hemoglobin that leads to chronic hemolysis and vaso-occlusive crisis. After decades of limited therapy options, crizanlizumab is a humanized monoclonal antibody approved by the Food and Drug Administration (FDA) in 2019 for sickle cell-related pain crises for patients 16 years of age and above. Although rare, infusion-related reactions, including painful crises, occurred in 3% as per the package insert. However, the data on how to deal with such reactions and about further treatment outcomes are limited as most patients stopped crizanlizumab after the reaction. Herein, we report the good outcome of 13 doses of crizanlizumab in a 19-year-old female patient with sickle cell disease on hydroxyurea, despite experiencing a severe infusion-related painful crisis during the second infusion. Additional benefits of crizanlizumab, in this case, were preventing new episodes of acute chest syndrome, quitting chronic narcotics use, and a remarkable improvement in quality of life and overall performance.
Crizanlizumab for the Prevention of Vaso-Occlusive Pain Crises in Sickle Cell Disease. [2022]Objective: To review the efficacy and safety of crizanlizumab (Adakveo) in the prevention of vaso-occlusive pain crises in sickle cell disease. Data Sources: An English-language literature search of PubMed, MEDLINE, and Ovid (1946 to January 2021) was completed using the terms crizanlizumab, SEG101, SelG1, and sickle cell disease. Manufacturer prescribing information, article bibliographies, and data from clinicaltrials.gov were incorporated in the reviewed data. Study Selection/Data Extraction: All studies registered on clinicaltrials.gov were incorporated in the reviewed data. Data Synthesis: Crizanlizumab is the first monoclonal antibody approved for sickle cell disease to reduce the frequency of vaso-occlusive crises. One phase 2 clinical trial and a post hoc analysis of the trial have been published. Relevance to Patient Care and Clinical Practice: Crizanlizumab is a monthly intravenous infusion approved by the Food and Drug Administration for patients with sickle cell disease 16 years of age and older to reduce the frequency of vaso-occlusive crises. Conclusion: Crizanlizumab appears to be an efficacious therapy for patients with sickle cell disease to reduce the frequency of vaso-occlusive crises. Concerns include drug cost and administration. Long-term benefits and risks have not been determined.
The European Medicines Agency Review of Crizanlizumab for the Prevention of Recurrent Vaso-Occlusive Crises in Patients With Sickle Cell Disease. [2021]Crizanlizumab is a monoclonal antibody that binds to P-selectin. On October 28, 2020, a conditional marketing authorization valid through the European Union (EU) was issued for crizanlizumab for the prevention of recurrent vaso-occlusive crises (VOCs) in patients with sickle cell disease aged 16 years or older. Crizanlizumab was evaluated in a phase 2, double-blind, placebo-controlled randomized multicenter trial comparing high-dose (5 mg/kg) crizanlizumab, low-dose (2.5 mg/kg) crizanlizumab and placebo in patients with a history of 2-10 VOCs in the previous year. Patients who were receiving concomitant hydroxycarbamide (HC) as well as those not receiving HC were included in the study. The primary endpoint of the trial was the annual rate of sickle cell-related pain crises as adjudicated by a central review committee. High-dose crizanlizumab led to a 45.3% lower median annual rate of sickle cell-related pain crises compared to placebo (P = 0.010), with no statistically significant difference for the low dose. Treatment with high-dose crizanlizumab led to similar incidences of adverse events (AEs), grade 3 AEs, and serious AEs compared to placebo. Most frequently observed AEs that occurred more often in the crizanlizumab arm compared to placebo were infusion related reactions (34.8% versus 21%), arthralgia (18.2% versus 8.1%), diarrhea (10.6% versus 3.2%), and nausea (18.2% versus 11.3%). The aim of this article is to summarize the scientific review of the application leading to regulatory approval in the EU.
Crizanlizumab: First Approval. [2020]Crizanlizumab (Adakveo®; crizanlizumab-tmca) is an intravenously administered monoclonal antibody developed by Novartis Pharmaceuticals for the prevention of vaso-occlusive crises (VOCs) in patients with sickle cell disease. Crizanlizumab binds to P-selectin, thereby blocking its interaction with P-selectin glycoprotein ligand-1. In November 2019, crizanlizumab received its first global approval in the USA, where it is indicated to reduce the frequency of VOCs in adults and paediatric patients aged ≥ 16 years with sickle cell disease. The drug is also under regulatory review in the EU for the prevention of VOCs in patients with sickle cell disease. The use of crizanlizumab (in combination with ruxolitinib) in myelofibrosis is also being evaluated in Australia, Spain, Germany and Hungary. This article summarizes the milestones in the development of crizanlizumab leading to this first approval for the reduction of VOCs in patients with sickle cell disease.
Systematic Review of Crizanlizumab: A New Parenteral Option to Reduce Vaso-occlusive Pain Crises in Patients with Sickle Cell Disease. [2021]Hydroxyurea, indicated for managing sickle cell anemia (SCA), and L-glutamine, indicated for treating sickle cell disease (SCD), were the only pharmacotherapeutic options in this patient population before the approval of crizanlizumab by the U.S. Food and Drug Administration in November 2019 to reduce vaso-occlusive crisis (VOC) frequency. This article reviews the evidence pertaining to crizanlizumab in SCD by searching records in Medline, Embase, and International Pharmaceutical Abstracts. Crizanlizumab, a P-selectin inhibitor, mitigates the microvascular vaso-occlusion in SCD. In the multicenter randomized double-blind SUSTAIN trial, a higher dose of crizanlizumab decreased the incidence of VOCs by 45% and prolonged the median time to the first and second VOC. A post hoc subgroup analysis demonstrated that the proportion of patients who had no VOC incidence during the study period was greater in the crizanlizumab group, and this benefit was consistent regardless of concomitant hydroxyurea use, prior categorized history of VOC frequency, or SCD genotype. Crizanlizumab had a safety profile comparable with placebo. Multiple ongoing clinical trials are trying to establish its roles in pediatric patients with SCD and its effects on alleviating other SCD-related complications. As the first parenteral option for SCD, providers need to formulate administration logistics to improve patients' access to crizanlizumab. Current available data suggest crizanlizumab is a promising agent to reduce VOC in patients with SCD.