IMPACTS Trial: Investigation of the Modulation of Phospholipase in Acute Chest Syndrome

IMPACTS Trial: Investigation of the Modulation of Phospholipase in Acute Chest Syndrome (Dose Escalation Study: Varespladib Infusion [A-001] for the Prevention of Acute Chest Syndrome in At-Risk Patients With Sickle Cell Disease and Vaso-occlusive Crisis)

The study will be conducted at 15-20 US centers in a randomized, placebo-controlled, double-blind fashion. Enrollees will be hospitalized sickle cell disease (SCD) patients at-risk for acute chest syndrome (ACS) based on the presence of vaso-occlusive crisis (VOC), fever (T ≥38.0°C) and serum sPLA2 concentration ≥50 ng/mL.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease; Acute Chest Syndrome; Vaso-occlusive Crisis
• Intervention / Treatment: Other: Placebo; Drug: A-001

Detailed Description

This is a double-blind randomized, parallel group, placebo-controlled dose escalation study (2 cohorts) in patients with sickle cell disease (SCD) and vaso-occlusive crisis (VOC) who are at-risk for development of acute chest syndrome (ACS) based on the combination of VOC, fever (T ≥38.0ºC), and a serum sPLA2 concentration ≥50 ng/mL.

The first group of patients will be randomized 2:1 to receive low dose A-001 or placebo as a 48-hour continuous infusion. Pharmacokinetic and clinical data from this group will undergo review by the Independent Data Monitoring Committee (IDMC). If there is no significant toxicity associated with A-001, then an additional group of patients will be enrolled and randomized 2:1 to high dose A-001 versus placebo as a 48-hour continuous infusion.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20060
      • Howard University Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Children's Healthcare of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27713
      • Duke University Comprehensive Sickle Cell Center
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Patients are eligible for inclusion if they meet the following criteria:

• Sickle cell variant (Hb SS, Hb SC, sickle β°-thalassemia, sickle β+-thalassemia)
• Pain consistent with vaso-occlusive crisis
• Elevated serum sPLA2 level (measured on-site)
• Fever
• Age ≥5 years (through adult)

Patients must NOT meet any of the following exclusion criteria:

• New lung infiltrate by chest radiography
• Pregnancy or breastfeeding
• Significant renal dysfunction
• Significant hepatic dysfunction
• Acute neurologic dysfunction
• Any medical condition for which transfusion may be needed imminently, and/or hemoglobin <5 g/dL
• Red blood cell transfusion within 30 days of entry into the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo
Experimental: A-001	Drug: A-001; A-001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the safety and tolerability of different doses of A 001 therapy when administered as a 2-day continuous infusion to sickle cell disease (SCD) patients at-risk for the acute chest syndrome (ACS).	Study end

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine the pharmacokinetic profile of A-001 in SCD patients	Study end
To confirm the ability of A-001 infusion to suppress serum sPLA2 activity in SCD patients with elevated serum sPLA2	Study end
To determine the efficacy of A-001 infusion in preventing ACS in SCD patients with the combination of vaso-occlusive crisis (VOC), fever, and elevated serum sPLA2	Study end

Collaborators and Investigators

• Sponsor: Anthera Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: February 9, 2007
• First Submitted That Met QC Criteria: February 9, 2007
• First Posted (Estimate): February 13, 2007

Study Record Updates

• Last Update Posted (Estimate): March 4, 2014
• Last Update Submitted That Met QC Criteria: January 30, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Syndrome; Anemia, Sickle Cell; Acute Chest Syndrome
• Other Study ID Numbers: AN-SCD1121