Phase II Randomized, Double-Blind, Placebo-Controlled Study of Intravenous Mucoid Exopolysaccharide Pseudomonas Aeruginosa Immune Globulin for Cystic Fibrosis

Sponsor

National Center for Research Resources (NCRR) (NIH)

Overall Status

Completed

CT.gov ID

NCT00004747

Collaborator

Vanderbilt University Medical Center (Other)

170

Enrollment

Study Details

Study Description

Brief Summary

OBJECTIVES: I. Assess the efficacy of monthly intravenous mucoid exopolysaccharide Pseudomonas aeruginosa immune globulin (MEP IGIV) given over 1 year in reducing the frequency of acute pulmonary exacerbation in patients with cystic fibrosis, mild to moderate pulmonary disease, and mucoid P. aeruginosa colonization.

Assess the effect of MEP IGIV on FEV1, sputum density of mucoid P. aeruginosa, and the quality of life in these patients.
Assess the safety of monthly MEP IGIV. IV. Assess population-based MEP IGIV pharmacokinetics during chronic therapy.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis Bacterial Infections	Drug: mucoid exopolysaccharide P. aeruginosa immune globulin IV	Phase 2

Detailed Description

PROTOCOL OUTLINE: This is a randomized, double-blind study. Patients are stratified by participating institution.

Patients are randomly assigned to 1 of 3 groups: low-dose intravenous mucoid exopolysaccharide Pseudomonas aeruginosa immune globulin (MEP IVIG), high-dose MEP IVIG, or placebo. Therapy is administered every 28 days for 12 months. Treatment is not initiated in the presence of an acute asthmatic attack.

Concurrent chronic suppressive antibiotics are permitted.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Masking:

Double

Primary Purpose:

Treatment

Study Start Date :

Jul 1, 1995

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

PROTOCOL ENTRY CRITERIA:

Disease Characteristics

Cystic fibrosis (CF) documented by pilocarpine iontophoresis sweat chloride greater than 60 mEq/L FEV1 30%-80% of predicted and within 20% of maximum values obtained in 12 months prior to entry Able to expectorate at least 1 g of sputum within 3 hours at screening
Mucoid Pseudomonas aeruginosa colonization documented in at least 2 serial expectorated sputum cultures in the year prior to entry Screening specimen meets requirement for 1 culture
Documented exacerbation of respiratory tract infection At least 1 hospitalization and/or course of parenteral or nebulized antibiotic therapy in each of the 2 years prior to entry
At least 2 serial spirometry tests over at least 6 months prior to entry FEV1 range no more than 15% relative to maximum value
None of the following within 6 months prior to entry: Pseudomonas (Burholderia) cepacia or atypical mycobacteria in respiratory tract Pulmonary hemorrhage with greater than 5% drop in hematocrit Pneumothorax requiring chest tube
No life-threatening CF sequelae, e.g.: Severe cirrhosis with ascites or bleeding Severe distal intestinal obstruction syndrome requiring cessation of oral intake Poorly controlled insulin-dependent diabetes with acetonuria

Prior/Concurrent Therapy

No concurrent participation in other investigational protocols
No prior investigational P. aeruginosa vaccine
At least 45 days since immune globulin or antibacterial monoclonal antibody
At least 4 weeks since investigational drugs
At least 2 weeks since systemic glucocorticoids
No requirement for systemic steroids during first 2 weeks of study

Patient Characteristics

Renal: Creatinine less than 2 mg/dL (1.5 mg/dL in patients under 50 kg)
No proteinuria
No hematuria
Cardiovascular: No cor pulmonale or other heart disease requiring chronic diuretics, afterload reduction, or cardiac glycoside therapy (e.g., digoxin)
Immunologic: Endogenous immunoreactive IgA at least 5 mg/dL
No hypersensitivity to immune globulin or human albumin
No primary or acquired immunodeficiency disease
Other: No clinical test abnormal on repeat and inconsistent with CF
No smoking 1 month prior to and during study
No suspected drug or alcohol abuse within 1 year prior to entry
No severe illness that precludes protocol participation
No disability, condition, or geographical location that would impair compliance
No psychiatric disorder, intellectual deficiency, or other condition that would limit informed consent
Negative pregnancy test required of fertile women
Medically acceptable contraception required of fertile women
Participating investigators, sub-investigators, study coordinators, and employees of participating investigators or immediate family members of any of these groups ineligible
Blood/body fluid analyses and other exams within 28 days prior to registration