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)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00434473

Enrollment

Registered

2007-02-13

Start date

2006-12-31

Completion date

2009-12-31

Last updated

2014-03-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Chest Syndrome, Sickle Cell Disease, Vaso-occlusive Crisis

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.

Interventions

DRUGA-001

A-001

OTHERPlacebo

Placebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

5 Years to No maximum

Healthy volunteers

Inclusion 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

Design outcomes

Primary

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

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

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026