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Oral Bacterial Extract for the Prevention of Wheezing Lower Respiratory Tract Illness (ORBEX)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02148796
Recruitment Status : Active, not recruiting
First Posted : May 28, 2014
Last Update Posted : April 27, 2021
Sponsor:
Information provided by (Responsible Party):
University of Arizona

Brief Summary:
The primary objective of this study is to evaluate if Broncho-Vaxom® given to high risk infants for 10 days, monthly, for two consecutive years can increase time to occurrence of the first episode of wheezing lower respiratory tract illness (WLRI) during a three year observation period off therapy.

Condition or disease Intervention/treatment Phase
Asthma Wheezing Drug: Broncho-Vaxom (BV) Other: Placebo Phase 2

Detailed Description:
This is a five year parallel arm, double-blind, placebo-controlled trial for the prevention of WLRI into the third to seventh year of life (30 to 78 mo inclusive) in young children (6-18 months old) at increased risk for asthma. The trial will be divided into 2 periods. During the initial treatment period (first and second years in the study) participants will receive Broncho- Vaxom® (3.5 mg) or placebo for ten days each month for two consecutive years. This period will allow the observation of key secondary outcomes while participants are receiving therapy. The second period (third through fifth years in the study) will be a three year observation of the time to occurrence of the first WLRI episode (primary outcome) while off study drug along with the secondary outcomes noted above. During both the treatment and observation periods, participants will be managed by study physicians using a rescue algorithm applied in the PEAK trial commensurate with the NAEPP Expert Panel Report (EPR) III guidelines.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 822 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: Randomized, Placebo-controlled, Multicenter Study to Assess the Efficacy, Safety and Tolerability of ORal Bacterial EXtract for the Prevention of Wheezing Lower Respiratory Tract Illness (ORBEX)
Actual Study Start Date : January 3, 2017
Estimated Primary Completion Date : December 31, 2025
Estimated Study Completion Date : December 31, 2025

Arm Intervention/treatment
Active Comparator: Broncho-Vaxom (BV)
One capsule of Broncho-Vaxom for children contains: 3.5 mg of lyophilized bacterial lysates of Haemophilus influenzae, Streptococcus (pneumonia, pyogenes and sanguinis (viridans)), Klebsiella (pneumoniae and ozaenae), Staphylococcus aureus and Moraxella catarrhalis. The content of the capsule will be mixed with a palatable liquid such as fruit juice.
Drug: Broncho-Vaxom (BV)
Active Ingredient: Lyophilised bacterial extract; Chemical Name: OM-85 BV; Strength: 3.5 mg; Excipients: bacterial extract, propyl gallate, sodium glutamate, mannitol, pregelatinised starch, magnesium stearate; Appearance: Blue and white capsule; Dosage Form: 3.5 mg capsule; Manufacturer: OM Pharma, Switzerland (OM stands for Omnia Medicamenta) Storage: Store in the original package
Other Names:
  • OM-85 BV VEGETAL
  • Broncho-Vaxom concentrate (bacterial lysate)

Placebo Comparator: Placebo
A placebo capsule will be used that will be indistinguishable from the active study drug.
Other: Placebo
A placebo capsule will be used that will be indistinguishable from the active study drug.




Primary Outcome Measures :
  1. The time to the occurrence of the first WLRI episode in the observation period while not receiving study drug [ Time Frame: ages 30 to 42 months at the end of treatment; ages 66 to 78 months at completion ]
    The time to the occurrence of the first WLRI episode in the observation period while not receiving study drug


Secondary Outcome Measures :
  1. The time to first WLRI during the two treatment years while receiving study drug [ Time Frame: ages 6 to 18 months at start of therapy; ages 30 to 42 months at completion ]
    The time to first WLRI during the two treatment years while receiving study drug

  2. The annualized rate of WLRI episodes during the two years while receiving study drug [ Time Frame: ages 6 to 18 months at start of therapy; ages 30 to 42 months at completion ]
    The annualized rate of WLRI episodes during the two years while receiving study drug

  3. The annualized rate of WLRI episodes during the observation period while not receiving study drug [ Time Frame: ages 30 to 42 months at the end of treatment; ages 66 to 78 months at completion ]
    The annualized rate of WLRI episodes during the observation period while not receiving study drug

  4. The annualized rate of severe wheezing respiratory tract illness (SWLRI) episodes during the two treatment years while receiving study drug. [ Time Frame: ages 6 to 18 months at start of therapy; ages 30 to 42 months at completion ]

    SWLRI episodes are defined as cough and wheezing > 24 hours AND any one of the following:

    • Use of more than 6 albuterol treatments in ≤48 hours.
    • Unscheduled care visit for acute wheezing in doctor's office, urgent care or emergency department -or- hospitalization for wheezing.
    • Use of systemic corticosteroid prescribed by a licensed medical provider for a wheezing illness with or without a clinical visit.
    • The annualized rate of SWLRI episodes during the two years while receiving study drug.

  5. The annualized rate of severe wheezing respiratory tract illness (SWLRI) episodes during the observation period while not receiving study drug. [ Time Frame: ages 30 to 42 months at the end of treatment; ages 66 to 78 months at completion ]
    The annualized rate of severe wheezing respiratory tract illness (SWLRI) episodes during the observation period while not receiving study drug.

  6. Asthma at the end of the observation period [ Time Frame: ages 30 to 42 months at the end of treatment; ages 66 to 78 months at completion ]

    Asthma at the end of the observation period defined by any of the following three elements:

    (a) a health care provider diagnosis of asthma with reports of: at least one episode of wheezing or asthma in the previous year or asthma controllers prescribed for at least 6 months during the previous year; or (b) >3 episodes of wheezing during the previous year 38 ("frequent wheezers"); or (c) any wheezing during the third observation year in children who wheezed during the first three years of life ("persistent wheezers").


  7. Safety and tolerability of Broncho-Vaxom® while receiving study drug during the two year treatment period. [ Time Frame: ages 6 to 18 months at start of therapy; ages 30 to 42 months at completion ]
    Safety and tolerability of Broncho-Vaxom® while receiving study drug during the two year treatment period

  8. Safety and tolerability of Broncho-Vaxom® while receiving study drug during the observation period. [ Time Frame: ages 30 to 42 months at the end of treatment; ages 66 to 78 months at completion ]
    Safety and tolerability of Broncho-Vaxom® while receiving study drug during the observation period, after study drug has been stopped.


Other Outcome Measures:
  1. The proportion of episode free days (EFD) annualized for each year of study. [ Time Frame: Treatment (2 yr) and observation periods ]
    shortness of breath, cough, chest retraction or tightness; 2) No unscheduled medical visits for respiratory symptoms AND 3) No use of any asthma medications, including albuterol before exercise.

  2. Time to first systemic corticosteroid course [ Time Frame: Treatment (2 yr) and observation periods ]
    Time to first systemic corticosteroid course

  3. Number of systemic corticosteroid courses [ Time Frame: Treatment (2 yr) and observation periods ]
    Number of systemic corticosteroid courses

  4. Cumulative systemic corticosteroid courses [ Time Frame: Treatment (2 yr) and observation periods ]
    Cumulative systemic corticosteroid courses

  5. Cumulative systemic corticosteroid dose [ Time Frame: Treatment (2 yr) and observation periods ]
    Cumulative systemic corticosteroid dose

  6. Cumulative time receiving controller inhaled corticosteroid (ICS) [ Time Frame: Treatment (2 yr) and observation periods ]
    Cumulative time receiving controller inhaled corticosteroid (ICS)

  7. Cumulative does of controller ICS [ Time Frame: Treatment (2 yr) and observation periods ]
    Cumulative does of controller ICS

  8. Cumulative time of receiving any controller medication (ICS, systemic steroid, or montelukast) [ Time Frame: Treatment (2 yr) and observation periods ]
    Cumulative time of receiving any controller medication (ICS, systemic steroid, or montelukast)

  9. Days with albuterol use [ Time Frame: Treatment (2 yr) and observation periods ]
    Days with albuterol use

  10. Urgent care/Emergency Department (ED)/Office visits/hospitalizations for respiratory illness analyzed separately and combined variable [ Time Frame: Treatment (2 yr) and observation periods ]
    Urgent care/ED/Office visits/hospitalizations for respiratory illness analyzed separately and combined variable

  11. Change in height and weight from baseline [ Time Frame: Treatment (2 yr) and observation periods ]
    Change in height and weight from baseline



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   6 Months to 18 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Adequate completion of informed consent process with written documentation. The participant's legally acceptable representative must have provided the appropriate written informed consent. Assent forms will not be used due to the age of the participant population; however, for procedures later in the study when participants are older, age appropriate assent will be obtained, if required by local Institutional Review Board (IRB).
  • Age: 6-18 months of age inclusive at randomization which means 5 to 17 months of age inclusive on entry into the one month run-in period. At least half of all enrolled children will be between 6 and 12 months of age at randomization.
  • Participants will meet at least one of the following criteria, which have been associated with an increased risk of wheezing respiratory illnesses and asthma: a) Parental history of asthma -or- b) Physician-diagnosed atopic dermatitis in the participant - or- c) Physician-diagnosed asthma in a blood sibling aged 4 years or more.
  • Participants may be either male or female.
  • Participants will have at least one parent/guardian who can communicate with the study staff to allow assessment of study outcomes. All study materials used by parent/guardian will be made available in English and in Spanish.

The child's parent/guardian must have a working direct contact telephone.

Exclusion Criteria:

  • Participants may not have had more than two prior WLRI episodes.
  • Participants may not have had any SWLRI episodes.
  • Participants may not have a physician's diagnosis of asthma.
  • Participants may not have a systemic illness (other than allergy) including (but not limited to) recurrent seizures, chronic gastroesophageal reflux (GER) requiring medical treatment, major congenital anomalies, physical and intellectual delay, cerebral palsy, chest surgery, tuberculosis or other chronic infections, primary or secondary immunodeficiency, gastrointestinal malformation or disease or cardiac disorder (except a hemodynamically insignificant atrial septal defect (ASD), ventricular septal defect (VSD) or benign heart murmur).
  • Participants may not have been born earlier than 36 weeks of gestation.
  • Participants may not have received oxygen for more than 5 days in the neonatal period, or received mechanical ventilation with the exclusion of ventilation during anesthesia for a minor surgical procedure.
  • Participants may not have significant neurodevelopmental delay.
  • Participants may not be below the 3rd percentile for weight.
  • Participants may not have any other chronic lung disease; e.g. chronic lung disease of prematurity (CLDP) or cystic fibrosis.
  • Participants may not have a history of any life-threatening respiratory illness that required intubation and mechanical ventilation.
  • The participant's family may not be expected to relocate out of study area within 3 years of the initiation of the study.
  • Participants may not have received inhaled or systemic corticosteroids for respiratory related illness ever, or for other conditions in the month prior to randomization.
  • Participants may not have ever received immunotherapy.
  • Participants may not have ever received i.v. gammaglobulins or systemic immunosuppressants.
  • Participants may not have received probiotics (Lactobacilli and Bifidobacteria) in medicinal form; (i.e. not including food), regularly for more than 4 months in the 6 to <12 mo age group or 6 months in the 12 to 18 month group prior to enrollment.
  • Participant has known sensitivity to any of the study products and any of the ingredients to be administered.
  • Participant has previously been randomized in this study. Participants who failed run-in and were not randomized may have study participation terminated and then be re-enrolled for a second run-in period.
  • Participant is currently enrolled in or has completed any other investigational device or drug study <30 days prior to screening, or is receiving other investigational agent(s).
  • Participant has a significant medical condition(s), anticipated need for major surgery during the study, or any other kind of disorder that may be associated with increased risk to the participant, or may interfere with study assessments, outcomes, or the ability to provide written informed consent or comply with study procedures, in the Investigator's opinion.
  • The one month run-in period will be used to evaluate adherence to study drug administration and electronic communication. At randomization the participant must continue to meet enrolment criteria and also have demonstrated 80% adherence to the placebo during treatment period; i.e. 8 out of 10 days and a75% response rate to weekly mobile phone text queries; i.e. 3 out of 4 weekly text queries.
  • Ongoing infection (of any organ system) at the time of randomization. This includes infections that are being adequately treated.
  • Unable or unlikely to complete study assessments or the study intervention poses undue risk to patient in the opinion of the Investigator.
  • Families will speak English and/or Spanish.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02148796


Locations
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United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016
University of Arizona
Tucson, Arizona, United States, 85724
United States, California
University of California San Francisco, Benioff Children's Hospital
Oakland, California, United States, 94609
United States, District of Columbia
Children's National Health System
Washington, District of Columbia, United States, 20037
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Boston Children's Hospital, Harvard University
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
United States, New York
Columbia University
New York, New York, United States, 10032
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27514
United States, Ohio
Cincinnati Children's Hospital & Medical Center
Cincinnati, Ohio, United States, 45229
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792-4108
Sponsors and Collaborators
University of Arizona
Investigators
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Principal Investigator: Fernando D Martinez, MD University of Arizona
Study Director: Wayne J Morgan, MD University of Arizona
Study Director: Dave T Mauger, PhD Penn State University, Data Coordinating Center
Publications:
Bousquet J, Anto J, Auffray C, Akdis M, Cambon-Thomsen A, Keil T, Haahtela T, Lambrecht BN, Postma DS, Sunyer J, Valenta R, Akdis CA, Annesi-Maesano I, Arno A, Bachert C, Ballester F, Basagana X, Baumgartner U, Bindslev-Jensen C, Brunekreef B, Carlsen KH, Chatzi L, Crameri R, Eveno E, Forastiere F, Garcia-Aymerich J, Guerra S, Hammad H, Heinrich J, Hirsch D, Jacquemin B, Kauffmann F, Kerkhof M, Kogevinas M, Koppelman GH, Kowalski ML, Lau S, Lodrup-Carlsen KC, Lopez-Botet M, Lotvall J, Lupinek C, Maier D, Makela MJ, Martinez FD, Mestres J, Momas I, Nawijn MC, Neubauer A, Oddie S, Palkonen S, Pin I, Pison C, Rancé F, Reitamo S, Rial-Sebbag E, Salapatas M, Siroux V, Smagghe D, Torrent M, Toskala E, van Cauwenberge P, van Oosterhout AJ, Varraso R, von Hertzen L, Wickman M, Wijmenga C, Worm M, Wright J, Zuberbier T. MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine. Allergy. 2011 May;66(5):596-604. doi: 10.1111/j.1398-9995.2010.02534.x. Epub 2011 Jan 24. Review.
De Prost Y - Clinical Study Report (BV-2002/1) Multicentric, randomized, double-blind, placebo-controlled study of the efficacy and safety of Broncho-Vaxom® (OM-85 BV) in children suffering from atopic dermatitis. - Clinical Study Report (30 January 2008).
FDA Center for Drug Evaluation and Research (CDER) - Orally Inhaled and Intranasal Corticosteroids: Evaluation of the Effects on Growth in Children. Guidance for Industry: March 2007.
NHIS (2011)] National Health Interview Survey Data - Current Asthma Population Estimates. National Center for Health Statistics (NCHS), Centers for Disease Control and Prevention Hyattsville, MD: http://www.cdc.gov/asthma/nhis/2011/data.htm
NHLBI. National Asthma Education and Prevention Program: Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma; NIH Publication Number 08-5846. October 2007.
Principi N - Clinical Study Report (BV-2005/01) Double-Blind, Placebo-Controlled, Randomised Clinical Study of Broncho-Vaxom in Children Suffering from Recurrent Upper Respiratory Tract Infections. - Clinical Study Report (2 October 2012a).
Principi N - Clinical Study Report (EBV09/01) Double-Blind, Placebo-Controlled, Randomised Clinical Study of Broncho-Vaxom® Drops in Children Suffering from Recurrent Respiratory Tract Infections. - Clinical Study Report (23 October 2012b).
Spertini F - Clinical Study Report (BV-2007/03) Efficacy of Broncho-Vaxom® in Allergic Rhinitis: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Study. - Clinical Study Report (31 July 2009)

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Responsible Party: University of Arizona
ClinicalTrials.gov Identifier: NCT02148796    
Other Study ID Numbers: ORBEX-BV2014/06
First Posted: May 28, 2014    Key Record Dates
Last Update Posted: April 27, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by University of Arizona:
Wheezing
Lower respiratory tract illness
Asthma
Atopy
Additional relevant MeSH terms:
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Respiratory Sounds
Signs and Symptoms, Respiratory
Broncho-Vaxom
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs