Abciximab (ReoPro) as a Therapeutic Intervention for Sickle Cell Vaso-Occlusive Pain Crisis

NCT01932554 | Withdrawn Phase 2 DMC

• 1 other identifier: SLU 23331
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether giving abciximab (ReoPro) to children with sickle cell disease who are hospitalized for acute pain crisis will improve their pain and shorten the time spent in the hospital, when compared with standard supportive care.

Conditions

Sickle Cell Disease; Hb-SS Disease With Vasoocclusive Pain; Hemoglobin SS Disease With Vasoocclusive Crisis; Other Sickle Cell Disease With Vaso-Occlusive Pain; Hemoglobin SS Disease With Crisis

Keywords

Sickle Cell Pain Crisis; Abciximab; Integrins; Cell Adhesion Molecules

Outcome Measures

Primary Outcomes (1)

• Duration of hospitalization

  Total duration from admission to the inpatient service until discharge order is written, measured in days.

  Duration of hospital stay, expected average of 5 days

Secondary Outcomes (4)

• Total narcotic dose

  Duration of hospital stay, expected average of 5 days

• Bleeding complications

  From randomization until 10 days following initial discharge from hospital

• Complications (other than bleeding) attributed to study drug

  From randomization until 3 months following initial discharge from hospital

• Readmission rate

  From discharge date until 3 months following initial discharge from hospital

Study Arms (2)

Abciximab

EXPERIMENTAL

Abciximab will be administered as initial bolus of dose of 0.25 mg/kg, delivered via syringe pump over 15 minutes, followed by a continuous infusion of 0.125 microgram/kg/min (max of 10 micrograms/min) infused over the next 12 hours. Infusion to start within 16 hours of admission. Patients will receive standard supportive care, including intravenous hydration, supplemental oxygen, incentive spirometry, ibuprofen, and parenteral narcotic pain medications (morphine, hydromorphone or fentanyl)

Drug: Abciximab; Other: Intravenous hydration; Drug: Ibuprofen; Drug: Parenteral narcotic; Other: Incentive spirometry; Other: Supplemental oxygen

Placebo

PLACEBO COMPARATOR

Inactive placebo will be administered as initial bolus followed by a continuous infusion over the next 12 hours, in syringes and volumes identical with the drug administered in the experimental arm. Infusion to begin within 16 hours of admission. Patients will receive standard supportive care, including intravenous hydration, supplemental oxygen, incentive spirometry, ibuprofen, and parenteral narcotic pain medications (morphine, hydromorphone or fentanyl)

Drug: Placebo; Other: Intravenous hydration; Drug: Ibuprofen; Drug: Parenteral narcotic; Other: Incentive spirometry; Other: Supplemental oxygen

Interventions

Abciximab DRUG

Abciximab will be administered as initial bolus of dose of 0.25 mg/kg, delivered via syringe pump over 15 minutes, followed by a continuous infusion of 0.125 microgram/kg/min (max of 10 micrograms/min) infused over the next 12 hours. Infusion to start within 16 hours of admission. All patients will receive standard supportive care measures.

Also known as: ReoPro

Abciximab

Placebo DRUG

Inactive placebo will be administered as initial bolus followed by a continuous infusion over the next 12 hours, in syringes and volumes identical with the drug administered in the experimental arm. Infusion to begin within 16 hours of admission. All patients will also receive standard supportive care measures.

Placebo

Intravenous hydration OTHER

intravenous hydration to provide total fluid intake of 1.25-1.5 times maintenance fluid requirements

Abciximab; Placebo

Ibuprofen DRUG

Scheduled ibuprofen,\~10 mg/kg every 6-8 hours

Also known as: Advil, Motrin

Abciximab; Placebo

Parenteral narcotic DRUG

Parenteral morphine administered by bolus or patient-controlled analgesia to maintain pain control. Hydromorphone or fentanyl will be used in patients who do not tolerate morphine.

Also known as: morphine, hydromorphone, Dilaudid, fentanyl

Abciximab; Placebo

Incentive spirometry OTHER

Patients will perform incentive spirometry every 2 hours while awake

Abciximab; Placebo

Supplemental oxygen OTHER

Supplemental oxygen by nasal cannula or mask will be provided if needed to maintain oxygen saturation of 92% or greater.

Abciximab; Placebo

Eligibility Criteria

• Age: 5 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of sickle cell disease (Hb SS, HbSC, HbS-β0-thalassemia)
• Age 5.00 to 24.99 years
• Pain consistent with vaso-occlusive crisis that meets the criteria for hospitalization and parenteral narcotics: moderate-severe pain unresponsive to oral medications (NSAIDS + narcotics) that has no alternative etiology (e.g., trauma)
• Platelet count \>100,000
• INR \<1.2, PTT \< 40 seconds
• Negative urine pregnancy test for females of child-bearing potential, including any female ≥10 years of age
• Informed consent by patient (≥18 years of age) or parent (if patient \<18 years of age); assent from patients 12-18 years of age
• Ability to start drug/placebo infusion within 16 hours of admission

You may not qualify if:

• History of stroke (either ischemic or hemorrhagic)
• Currently receiving anticoagulation medication (heparin within 1 week, Coumadin within 3 weeks) or medication with irreversible anti-platelet effect (e.g., aspirin, ticlopidine) within 14 days
• Red cell transfusion within 60 days
• Major surgery within 30 days
• Treatment with hydroxyurea within 30 days (due to evidence that hydroxyurea can reverse platelet activation in patients with SCD)
• Tmax ≥ 102.0o F without concomitant signs of infection, or ≥ 100.4o F with any finding suggestive of bacterial infection, including acute chest syndrome (fever, respiratory symptoms, and new infiltrate on chest X-ray)
• Active internal bleeding
• Known allergy to abciximab or murine proteins
• Recent (within 6 weeks) gastrointestinal or genitourinary bleeding of clinical significance
• Bleeding diathesis
• History of vasculitis
• Intracranial neoplasm, arteriovenous malformation or aneurysm
• Severe uncontrolled hypertension
• Patients who previously participated in the study must be excluded due to the increased risk of severe thrombocytopenia.

Sponsors & Collaborators

• St. Louis University: lead
• Janssen Services, LLC: collaborator

Study Sites (1)

Cardinal Glennon Children's Medical Center

St Louis, Missouri, 63104, United States

Location

Related Publications (13)

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  PMID: 7993409 BACKGROUND

• Platt OS, Thorington BD, Brambilla DJ, Milner PF, Rosse WF, Vichinsky E, Kinney TR. Pain in sickle cell disease. Rates and risk factors. N Engl J Med. 1991 Jul 4;325(1):11-6. doi: 10.1056/NEJM199107043250103.

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  PMID: 12614204 BACKGROUND

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  PMID: 14693325 BACKGROUND

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  PMID: 18024615 BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell; Vaso-Occlusive Crises

Interventions

Abciximab; Ibuprofen; Morphine; Hydromorphone; Fentanyl

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Piperidines; Heterocyclic Compounds, 1-Ring

Study Officials

• William S Ferguson, MD

  St. Louis University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: August 19, 2013
• First Posted: August 30, 2013
• Study Start: November 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: March 26, 2015

Record last verified: 2015-03

Locations

US (1)