Prospective Evaluation of the Efficacy of Palivizumab Administration in Children Born at 29-32 Weeks of Gestation

Protocol Synopsis: There is a link between early RSV infection and chronic respiratory morbidity.

Hypothesis: Palivizumab administration may result in decreased AHR and lower respiratory morbidity.

Primary objective: to evaluate prospectively the effect of palivizumab on airway reactivity (AHR) in children born at 29-32 weeks.

Secondary objective: to assess prospectively the effect of palivizumab on respiratory morbidity airway inflammation and allergy in children born at 29-32 weeks.

Inclusion criteria: premature babies 29-32 weeks of gestation born during 2007 and 2010.

Exclusion criteria: Any mechanical ventilation or chronic diseases, e.g., bronchopulmonary dysplasia (BPD), cystic fibrosis (CF), congenital heart disease, congenital anomalies, known immunodeficiency, or receipt of other RSV investigative vaccines or therapies.

Primary end points: Airway reactivity as assessed by methacholine challenge test with determination of PC20.

Secondary end points: Respiratory morbidity as assessed by questionnaire and telephone interviews. Additionally, IGE, eosinophil count, and exhaled NO will be evaluated.

Sample size: 74 participants; Group I - 37 premature babies at 29-32 weeks of gestation born during 2007-2008 (before approval of Synagis for this group in Israel). Group II - 37 premature babies 29-32 weeks of gestation born during 2009-2010 (after approval of Synagis for this group in Israel).

Statistics: A sample size of 37 patients was calculated as necessary to detect a difference of 0.5 SD in AHR for a 2-sided tail, with a power of 80%. Demographics and baseline characteristics will be compared using 1-way analysis of variance for quantitative variables and Fisher's exact test for categorical variables.

Study Overview

• Status: Completed
• Conditions: Bronchial Hyperreactivity; Infant, Premature
• Intervention / Treatment: Other: Methacholine Challenge Test (MCT); Other: Monthly telephone contact; Other: Visits to the study site; Other: Blood Test; Other: Fractional exhaled nitric oxide

Detailed Description

Protocol Synopsis: There is a link between early RSV infection and chronic respiratory morbidity.

Hypothesis: Palivizumab administration may result in decreased AHR and lower respiratory morbidity.

Primary objective: to evaluate prospectively the effect of palivizumab on airway reactivity (AHR) in children born at 29-32 weeks.

Secondary objective: to assess prospectively the effect of palivizumab on respiratory morbidity airway inflammation and allergy in children born at 29-32 weeks.

Inclusion criteria: premature babies 29-32 weeks of gestation born during 2007 and 2010.

Exclusion criteria: Any mechanical ventilation or chronic diseases, e.g., bronchopulmonary dysplasia (BPD), cystic fibrosis (CF), congenital heart disease, congenital anomalies, known immunodeficiency, or receipt of other RSV investigative vaccines or therapies.

Primary end points: Airway reactivity as assessed by methacholine challenge test with determination of PC20.

Secondary end points: Respiratory morbidity as assessed by questionnaire and telephone interviews. Additionally, IGE, eosinophil count, and exhaled NO will be evaluated.

Sample size: 74 participants; Group I - 37 premature babies at 29-32 weeks of gestation born during 2007-2008 (before approval of Synagis for this group in Israel). Group II - 37 premature babies 29-32 weeks of gestation born during 2009-2010 (after approval of Synagis for this group in Israel).

Statistics: A sample size of 37 patients was calculated as necessary to detect a difference of 0.5 SD in AHR for a 2-sided tail, with a power of 80%. Demographics and baseline characteristics will be compared using 1-way analysis of variance for quantitative variables and Fisher's exact test for categorical variables..

• Study Type: Observational
• Enrollment (Actual): 42

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel, 32000
    • Rambam Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 7 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Premature babies 29-32 weeks of gestation born during 2007 and 2010

Description

Inclusion Criteria:

• Premature babies 29-32 weeks of gestation born during 2007 and 2010

Exclusion Criteria:

• Any mechanical ventilation
• Chronic diseases, e.g., bronchopulmonary dysplasia (BPD), cystic fibrosis (CF), congenital heart disease, congenital anomalies
• Known immunodeficiency
• Receipt of other RSV investigative vaccines or therapies

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Born in 2007-2008; Methacholine Challenge Test (MCT). Monthly telephone contact. Visits to the study site. Fractional exhaled nitric oxide. Blood test.	Other: Methacholine Challenge Test (MCT); MCT challenge with determination of methacholine concentration that causes a 20% decrease from baseline FEV1 (forced expiratory volume in the 1st second of expiration) - PC20-FEV1 - is a well-documented method of assessing bronchial hyper-reactivity (BHR) in both adults and children. Our group has shown that the determination of PC20 by spirometry is feasible in preschool children. MCT is considered safe in this age group and our group has extensive experience with no adverse events. In the current study MCT will be performed (for the first time) in premature babies born at 30-32 weeks of gestation during 2008-2009 when they reach the age of 3-4 years (2011 and 2012, respectively). The results of MCT of the two groups will be compared.; Other: Monthly telephone contact; Monthly telephone contact with the parents/caregivers will be scheduled from enrollment until the final visit at age 3-4 years. Subject illnesses and other medical events occurring during the past month will be recorded at each monthly follow-up.; Other: Visits to the study site; Visits to the study site will be conducted at 6-month intervals in which physicians will record intercurrent doctor visits, emergency visits, and hospitalizations for respiratory symptoms.; Other: Blood Test; For assessing IgE levels, Eosinophils count and cytokines levels; Other: Fractional exhaled nitric oxide; Participant blow tidal volume for determination of exhaled NO in Exhaled breath.
Born in 2009-2010; Methacholine Challenge Test (MCT). Monthly telephone contact. Visits to the study site. Fractional exhaled nitric oxide. Blood test.	Other: Methacholine Challenge Test (MCT); MCT challenge with determination of methacholine concentration that causes a 20% decrease from baseline FEV1 (forced expiratory volume in the 1st second of expiration) - PC20-FEV1 - is a well-documented method of assessing bronchial hyper-reactivity (BHR) in both adults and children. Our group has shown that the determination of PC20 by spirometry is feasible in preschool children. MCT is considered safe in this age group and our group has extensive experience with no adverse events. In the current study MCT will be performed (for the first time) in premature babies born at 30-32 weeks of gestation during 2008-2009 when they reach the age of 3-4 years (2011 and 2012, respectively). The results of MCT of the two groups will be compared.; Other: Monthly telephone contact; Monthly telephone contact with the parents/caregivers will be scheduled from enrollment until the final visit at age 3-4 years. Subject illnesses and other medical events occurring during the past month will be recorded at each monthly follow-up.; Other: Visits to the study site; Visits to the study site will be conducted at 6-month intervals in which physicians will record intercurrent doctor visits, emergency visits, and hospitalizations for respiratory symptoms.; Other: Blood Test; For assessing IgE levels, Eosinophils count and cytokines levels; Other: Fractional exhaled nitric oxide; Participant blow tidal volume for determination of exhaled NO in Exhaled breath.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Airway reactivity	As assessed by methacholine challenge test with determination of PC20 and inflammatory mediators in exhaled breath condensate.	Between the 3 to 4 years-of-age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory morbidity	Monthly telephone contact with the parents/caregivers will be scheduled from enrollement until the final visit at age 3-4 years. Visits to the study site will be conducted at 6-month intervals. Subject illnesses and other medical events occurring during the past month will be recorded at each monthly follow-up. At 6-month intervals, physicians will record intercurrent doctor visits, emergency visits, and hospitalizations for respiratory symptoms.	every month
IgE	in pereferal Blood count	Between the 3 to 4 years-of-age
Eosinophil count	in pereferal Blood count	Between the 3 to 4 years-of-age
skin tests for inhaled allergens		Between the 3 to 4 years-of-age

Collaborators and Investigators

• Sponsor: Rambam Health Care Campus

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: January 3, 2011
• First Submitted That Met QC Criteria: January 3, 2011
• First Posted (Estimate): January 4, 2011

Study Record Updates

• Last Update Posted (Estimate): November 10, 2015
• Last Update Submitted That Met QC Criteria: November 8, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Palivizumab; EBC; MCT; Airway Hyperreactivity
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchial Hyperreactivity; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Protective Agents; Cholinergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Miotics; Parasympathomimetics; Bronchoconstrictor Agents; Muscarinic Agonists; Nitric Oxide; Methacholine Chloride
• Other Study ID Numbers: Evaluation of Palivizumab