Clinical trial NCT00434473: IMPACTS Trial: Investigation of the Modulation of Phospholipase in Acute Chest Syndrome
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sickle Cell Disease
Vaso-occlusive Crisis
Acute Chest Syndrome
Lead sponsor: Anthera Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2007-02-13
Enrollment: 30
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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).
timeFrame: Study end
Secondary outcomes:
measure: To determine the pharmacokinetic profile of A-001 in SCD patients
timeFrame: Study end
measure: To confirm the ability of A-001 infusion to suppress serum sPLA2 activity in SCD patients with elevated serum sPLA2
timeFrame: Study end
measure: 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
timeFrame: Study end
Other outcomes:
Locations:
city: Washington
country: United States
facility: Howard University Hospital
state: District of Columbia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Comprehensive Sickle Cell Center
state: North Carolina
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
References: