Clinical trial NCT01995175: 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
Official title: A Prospective, Epidemiological Study to Assess the Disease Burden of RSV Associated, Suspected LRTIs From 0 to 2 Years and Population Attributable Risk Percent of RSV LRTI on the Development of Recurrent Wheeze and Asthma From 0 to 6 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Respiratory Syncytial Virus
Keywords: Asthma
Respiratory Syncytial virus
Cohort study
Quarterly phone contacts
Wheeze
New born
Lower Respiratory Tract Infection
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2013-11-26
Enrollment: 2409
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Detailed description: New born infants from various countries over the world will be followed up for up to two years for the occurrence of Lower Respiratory Tract Infections. Through active and passive surveillance, any suspected case will be identified, assessed during an examination visit and followed up until completion through a diary card. Full symptomology will be assessed during the examination visit. The disease course and all healthcare utilization will be subsequently collected through a two-week diary card and contact with ay healthcare providers involved in management of the disease. RSV detection will occur through quantitative PCR of collected nasal swabs. A baseline cord blood serum sample of all subjects and a follow-up blood serum sample from a sub-cohort will also be collected to assess antibody levels at various points in time and in relation to risk of RSV LRTI.

For extension period, pertaining to wheeze and asthma (Epoch 002): Subjects' parent(s)/LAR(s) will be asked to re-consent and subjects will be followed up through quarterly contacts up to the age of 6 years. Data collection will also occur from medical charts retrospectively for those who have a gap period between the end of the primary study and providing re-consent for the extension. The extension involves enrolment visit (at 2nd birthday \[on completion of primary study or as soon as possible thereafter\]) and quarterly surveillance contacts.

Eligibility criteria: Inclusion Criteria:

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).

Exclusion Criteria:

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.

Primary outcomes:
measure: Incidence Rates of First Episode of Respiratory Syncytial Virus (RSV) Respiratory Tract Infection (RTI) [Period 1]
timeFrame: From birth up to 2 years of age
measure: Number of Subjects Hospitalized for RSV [Period 1]
timeFrame: From birth up to 2 years of age
measure: Incidence Rates of RSV Lower Respiratory Tract Infection (LRTI) or Severe LRTI as Defined by the LRTI Case Definition and Severity Scale [Period 1]
timeFrame: From birth up to 2 years of age
measure: Number of RSV LRTI or Severe LRTI Episodes as Defined by the GlaxoSmithKline (GSK) LRTI Case Definition [Period 1]
timeFrame: From birth up to 2 years of age
measure: Number of RSV LRTI or Severe LRTI Episodes as Defined by the Existing Comparator LRTI Case Definition (WHO [Modjarrad 2015]) [Period 1]
timeFrame: From birth up to 2 years of age
measure: Number of RSV LRTI or Severe LRTI Episodes as Defined by the Existing Comparator LRTI Case Definition (Nokes et al.) [Period 1]
timeFrame: From birth up to 2 years of age
Secondary outcomes:
measure: Levels of RSV-A and B Neutralizing Antibodies in the Cord Blood [Period 1]
timeFrame: At birth (Month 0)
measure: Levels of RSV-A and B Neutralizing Antibodies in the Blood Serum [Period 1]
timeFrame: At 2, 4, 6, 12, 18 and 24 months of age
measure: GMTs of RSV A and B Neutralizing Antibodies in the Cord Blood by Subjects Classified According to Non-overlapping Disease Severity Categories [Period 1]
timeFrame: At Month 0
measure: GMTs of RSV A and B Neutralizing Antibodies by Subjects Classified According to Non-overlapping Disease Severity Categories [Period 1]
timeFrame: During the first 6 months of life
measure: Number of WHO LRTI Episodes by Age Categories [Period 1]
timeFrame: From birth up to 2 years of life
measure: Number of WHO Severe LRTI Cases by Age Categories [Period 1]
timeFrame: From birth up to 2 years of life
measure: Incidence Rates of First Episode of Medically Attended Wheeze [Period 2]
timeFrame: From 2 years of age up to 6 years of age
measure: Incidence Rates of First Episode of Wheeze or Asthma Requiring Hospital Admission [Period 2]
timeFrame: From 2 years of age up to 6 years of age
measure: Incidence Rates of First Episode of Reported Wheeze With Use of Any Medication [Period 2]
timeFrame: From 2 years of age up to 6 years of age
Other outcomes:
Locations:
city: Oakland
country: United States
facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: Santa Clara
country: United States
facility: GSK Investigational Site
state: California
city: Walnut Creek
country: United States
facility: GSK Investigational Site
state: California
city: Syracuse
country: United States
facility: GSK Investigational Site
state: New York
city: Roy
country: United States
facility: GSK Investigational Site
state: Utah
city: Syracuse
country: United States
facility: GSK Investigational Site
state: Utah
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Ciudad de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Rio Cuarto
country: Argentina
facility: GSK Investigational Site
city: Dhaka
country: Bangladesh
facility: GSK Investigational Site
city: Halifax
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Kokkola
country: Finland
facility: GSK Investigational Site
city: Oulu
country: Finland
facility: GSK Investigational Site
city: Pori
country: Finland
facility: GSK Investigational Site
city: Seinajoki
country: Finland
facility: GSK Investigational Site
city: San Pedro Sula
country: Honduras
facility: GSK Investigational Site
city: San Pedro Sula
country: Honduras
facility: GSK Investigational Site
city: Soweto
country: South Africa
facility: GSK Investigational Site
state: Gauteng
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Khon Kaen
country: Thailand
facility: GSK Investigational Site
city: Pathum Thani
country: Thailand
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.