A Prospective, Epidemiological Study to Assess the Disease Burden of Respiratory Syncytial Virus Associated, Suspected Lower Respiratory Tract Infections in Newborns, From 0 to 2 Years of Age and Risk of Development of Wheeze and Asthma From 0 to 6 Years of Age

NCT01995175 | Completed Results

• 1 other identifier: 200150
• Study Type: interventional
• Target: 2,409
• Locations: 8 countries
• Sites: 23

Brief Summary

The purpose of this study is to assess the incidence and associated healthcare utilization of RSV-associated, suspected LRTI in a general population of infants from birth up to 2 years of age, and also to assess the accuracy of a newly developed LRTI case definition and severity scale compared to two existing definitions. The study will also assess the population attributable risk percent of RSV LRTI on the development of wheeze and asthma from 0 to 6 years of age.

Conditions

Respiratory Syncytial Virus

Keywords

Asthma; Respiratory Syncytial virus; Cohort study; Quarterly phone contacts; Wheeze; New born; Lower Respiratory Tract Infection

Outcome Measures

Primary Outcomes (6)

• Incidence Rates of First Episode of Respiratory Syncytial Virus (RSV) Respiratory Tract Infection (RTI) [Period 1]

  The incidence rate was calculated by dividing the number of subjects reporting first episode over the follow-up period, to the total person-years. Detection of the RSV-infection was performed by reverse transcription quantitative real time polymerase chain reaction (RT-qPCR ) assay on ribonucleic acids (RNA) extracted from nasal swabs. Number of suspected RSV RTI cases were tabulated.

  From birth up to 2 years of age

• Number of Subjects Hospitalized for RSV [Period 1]

  Healthcare utilization included primary, secondary and tertiary care settings such as self-care with Over-The-Counter \[OTC\] drugs, general practitioner \[GP\] visits, emergency room \[ER\] visits, hospital visits, etc. Note: This outcome measure presents results only for the more severe events of healthcare utilization - RSV hospitalization. Results for other causes (non-RSV) hospitalization and healthcare utilization for other settings were not calculated, as data were not available.

  From birth up to 2 years of age

• Incidence Rates of RSV Lower Respiratory Tract Infection (LRTI) or Severe LRTI as Defined by the LRTI Case Definition and Severity Scale [Period 1]

  The incidence rate was calculated by dividing the number of subjects reporting first episodes over the follow-up period, to the total person-years. LRTI Case definition by WHO (Modjarrad 2015): LRTI is diagnosed when a child \<5 years presents with cough and/or difficulty in breathing has the following symptoms: Fast breathing, (\>60 per minute in a child \<2 m, \>50 per minute in a child 2 to 11 m and \>40 per minute in a child 12 to 59 m) or Oxygen saturation \<95% by pulse oximetry. Severe LRTI is diagnosed when an infant with RSV LRTI has oxygen saturation\<93% or lower chest wall drawing.

  From birth up to 2 years of age

• Number of RSV LRTI or Severe LRTI Episodes as Defined by the GlaxoSmithKline (GSK) LRTI Case Definition [Period 1]

  LRTI Case definition by GSK: LRTI is diagnosed when a child \<5 years presents with cough or runny or blocked nose and oxygen saturation \<95% with a respiratory rate ≥ 60/minute (\< 2 months of age); ≥ 50/minute (2 to 11 months of age); ≥ 40/minute (12 to 24 months of age) and has RSV infection, confirmed on nasal swab positive for RSV A or B by quantitative polymerase chain reaction (qPCR). Severe LRTI case definition by GSK: Child with LRTI and oxygen saturation \< 92%, OR Difficulty breathing leading to: Irritability/agitation, or Lethargy/sleepiness, or Severe chest indrawing, or Reduced/no vocalization, or Apnoea \> 20 sec, or Cyanosis, or Stop feeding well/dehydration.

  From birth up to 2 years of age

• Number of RSV LRTI or Severe LRTI Episodes as Defined by the Existing Comparator LRTI Case Definition (WHO [Modjarrad 2015]) [Period 1]

  LRTI is diagnosed when a child \<5 years presents with cough and/or difficulty in breathing has the following symptoms: Fast breathing, (\>60 per minute in a child \<2 m, \>50 per minute in a child 2 to 11 m and \>40 per minute in a child 12 to 59 m) or Oxygen saturation \<95% by pulse oximetry. Severe LRTI is diagnosed when a child has LRTI and Oxygen saturation \<93% by pulse oximetry and/or lower chest wall in-drawing.

  From birth up to 2 years of age

• Number of RSV LRTI or Severe LRTI Episodes as Defined by the Existing Comparator LRTI Case Definition (Nokes et al.) [Period 1]

  LRTI is diagnosed when a child has a history of acute cough or difficulty in breathing and greater than or equal to (≥) 1 of the following: Fast breathing for age (≥ 60 breaths/minimum if the child is \< 2 m ≥ 50 breaths/minimum if the child is 2-11 m). Indrawing, or Low oxygen saturation (\< 90%) by pulse oximetry or inability to feed (prostration or unconsciousness), when accompanied by a clinical diagnosis of LRTI or bronchiolitis. Severe LRTI is diagnosed when a child has Indrawing, or Low oxygen saturation (\< 90%) by pulse oximetry or inability to feed (prostration or unconsciousness), when accompanied by a clinical diagnosis of LRTI or bronchiolitis.

  From birth up to 2 years of age

Secondary Outcomes (9)

• Levels of RSV-A and B Neutralizing Antibodies in the Cord Blood [Period 1]

  At birth (Month 0)

• Levels of RSV-A and B Neutralizing Antibodies in the Blood Serum [Period 1]

  At 2, 4, 6, 12, 18 and 24 months of age

• GMTs of RSV A and B Neutralizing Antibodies in the Cord Blood by Subjects Classified According to Non-overlapping Disease Severity Categories [Period 1]

  At Month 0

• GMTs of RSV A and B Neutralizing Antibodies by Subjects Classified According to Non-overlapping Disease Severity Categories [Period 1]

  During the first 6 months of life

• Number of WHO LRTI Episodes by Age Categories [Period 1]

  From birth up to 2 years of life

Study Arms (1)

Overall Group

OTHER

Newborn subjects followed up for Lower Respiratory Tract Infections (LRTI) symptoms from birth until they are 2 years of age and for incidence of wheeze and asthma up to 6 years of age.

Procedure: Nasal swab sampling; Procedure: Blood sampling; Other: Diary cards

Interventions

Nasal swab sampling PROCEDURE

Nasal swab samples will be collected from subjects at each examination visit, if they develop respiratory tract infection symptoms with difficulty in breathing and are called for an examination visit in the study.

Overall Group

Blood sampling PROCEDURE

A single blood sample will be collected from a sub-cohort consisting of the first 2000 enrolled subjects when they are either 2, 4, 6, 12, 18 or 24 months old.

Overall Group

Diary cards OTHER

Diary cards will be provided to parents or LARs of the subjects to record RTI/LRTI, wheeze and asthma symptoms.

Overall Group

Eligibility Criteria

• Age: Up to 6 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Before birth:
• Subject whose parent(s)/Legally Acceptable Representative(s) (LARs), in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written informed consent (including consent to obtain a cord blood sample at birth) obtained from the parent(s)/LAR(s) of the subject.
• After Birth:
• Subject for whom updated and re-signed informed consent and confirmation of eligibility is available not later than 5 working days after birth.
• Cord blood sample collection of at least 3 mL, at birth.
• For extension period:
• Subject is enrolled at a study site that is participating in the extension period follow-up.
• Subject whose parent(s)/LAR(s), in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written informed consent (or witnessed thumb printed consent in case of an illiterate subject) obtained from the parent(s)/LAR(s) of the subject.
• Previous participation in the primary study (from birth up to the age of 2 years).

You may not qualify if:

• Before birth:
• Subject expected to become Child in care
• Subjects whose parent(s)/LAR(s) are below the age of 18 or the legal consenting age of the respective country if this is higher.
• After Birth:
• Child in care
• Newborn with a gestational age of less than 28 weeks.
• Subjects with any congenital condition that will require an expected postnatal stay in hospital of more than 12 consecutive weeks.
• Subjects with major congenital defects or serious chronic illness limiting life expectancy to less than 5 years.
• Subjects with any confirmed or suspected immunosuppressive or immunodeficient condition (including positive infection with human immunodeficiency virus \[HIV\]), based on medical history, physical examination or positive test result.
• For extension period:
• Child in care.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (23)

GSK Investigational Site

Oakland, California, 94611, United States

Location

GSK Investigational Site

Sacramento, California, 95815, United States

Location

GSK Investigational Site

Sacramento, California, 95823, United States

Location

GSK Investigational Site

Santa Clara, California, 95051, United States

Location

GSK Investigational Site

Walnut Creek, California, 94596, United States

Location

GSK Investigational Site

Syracuse, New York, 13210, United States

Location

GSK Investigational Site

Roy, Utah, 84067, United States

Location

GSK Investigational Site

Syracuse, Utah, 84075, United States

Location

GSK Investigational Site

Seattle, Washington, 98105, United States

Location

GSK Investigational Site

Ciudad de Buenos Aires, Buenos Aires, C1431FWO, Argentina

Location

GSK Investigational Site

Río Cuarto, 5800, Argentina

Location

GSK Investigational Site

Dhaka, 1000, Bangladesh

Location

GSK Investigational Site

Halifax, Nova Scotia, B3K 6R8, Canada

Location

GSK Investigational Site

Kokkola, 67100, Finland

Location

GSK Investigational Site

Oulu, 90220, Finland

Location

GSK Investigational Site

Pori, 28100, Finland

Location

GSK Investigational Site

Seinäjoki, 60100, Finland

Location

GSK Investigational Site

San Pedro Sula, 21101, Honduras

Location

GSK Investigational Site

San Pedro Sula, 21102, Honduras

Location

GSK Investigational Site

Soweto, Gauteng, 2013, South Africa

Location

GSK Investigational Site

Bangkok, 10330, Thailand

Location

GSK Investigational Site

Khon Kaen, 40002, Thailand

Location

GSK Investigational Site

Pathum Thani, 12120, Thailand

Location

Related Publications (3)

• Madhi SA, Ceballos A, Cousin L, Domachowske JB, Langley JM, Lu E, Puthanakit T, Ramet M, Tan A, Zaman K, Anspach B, Bueso A, Cinconze E, Colas JA, D'Andrea U, Dieussaert I, Englund JA, Gandhi S, Jose L, Kim JH, Klein NP, Laajalahti O, Mithani R, Ota MOC, Pinto M, Silas P, Stoszek SK, Tangsathapornpong A, Teeratakulpisarn J, Virta M, Cohen RA. Population Attributable Risk of Wheeze in 2-<6-Year-old Children, Following a Respiratory Syncytial Virus Lower Respiratory Tract Infection in The First 2 Years of Life. Pediatr Infect Dis J. 2025 May 1;44(5):379-386. doi: 10.1097/INF.0000000000004447. Epub 2024 Jul 1.

  PMID: 38985986 DERIVED

• Englund JA, Cohen RA, Bianco V, Domachowske JB, Langley JM, Madhi SA, Zaman K, Bueso A, Ceballos A, Cousin L, Gandhi S, Gruselle O, Jose L, Klein NP, Koen A, Puthanakit T, Shi M, Silas P, Tangsathapornpong A, Teeratakulpisarn J, Vesikari T, Haars G, Leach A, Stoszek SK, Dieussaert I. Evaluation of Clinical Case Definitions for Respiratory Syncytial Virus Lower Respiratory Tract Infection in Young Children. J Pediatric Infect Dis Soc. 2023 May 31;12(5):273-281. doi: 10.1093/jpids/piad028.

  PMID: 37142551 DERIVED

• Langley JM, Bianco V, Domachowske JB, Madhi SA, Stoszek SK, Zaman K, Bueso A, Ceballos A, Cousin L, D'Andrea U, Dieussaert I, Englund JA, Gandhi S, Gruselle O, Haars G, Jose L, Klein NP, Leach A, Maleux K, Nguyen TLA, Puthanakit T, Silas P, Tangsathapornpong A, Teeratakulpisarn J, Vesikari T, Cohen RA. Incidence of Respiratory Syncytial Virus Lower Respiratory Tract Infections During the First 2 Years of Life: A Prospective Study Across Diverse Global Settings. J Infect Dis. 2022 Aug 26;226(3):374-385. doi: 10.1093/infdis/jiac227.

  PMID: 35668702 DERIVED

MeSH Terms

Conditions

Asthma; Respiratory Sounds

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

lr24921@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2013
• First Posted: November 26, 2013
• Study Start: December 12, 2013
• Primary Completion: October 3, 2017
• Study Completion: November 3, 2021
• Last Updated: November 29, 2022
• Results First Posted: February 15, 2019

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

AR (2); ZA (1); US (9); CA (1); TH (3); FI (4); HO (2); BA (1)