Nasal and Bronchial Absorption Sampling in RSV Bronchiolitis (RSV-SAM)

Validation of Nasal and Bronchial Absorption Sampling Methods for the Assessment of RSV Bronchiolitis in Babies and Children

This study will compare the novel methods of NS and BS with the standard technique of nasophayngeal aspiration (NPA) and routine ETT suction. We shall assess the samples for diagnosis of RSV, viral load and immune responses in the airways of babies with RSV infection. We shall also assess the genetics of babies included in this study, to see if they may be vulnerable to RSV infection.

Study Overview

• Status: Completed
• Conditions: Respiratory Failure; Bronchiolitis; RSV Infection; Bronchiolitis, Viral
• Intervention / Treatment: Diagnostic test: Nasal and Bronchial Sampling

Detailed Description

In conjunction with a specialist medical device manufacturing company (Hunt Developments (Midhurst, West Sussex) we have produced novel nasosorption and bronchosorption kits that have CE marking. Both nasosorption and bronchosorption methods use synthetic absorptive matrix (SAM) strips: that look and feel like blotting paper, and will be placed onto the mucosal surface. These are comfortable to use and can be used at frequent intervals over extended periods of time. This non-invasive technique is ideal for infants and children, and it is possible to obtain neat mucosal lining fluid (MLF) even from normal healthy noses. The eluates contain cytokines and chemokines at high detectable levels on multiplex immunoassay.

We would like to use these SAMs to take MLF samples from the nasal and bronchial mucosal surfaces to see if these novel techniques can overcome the problems with current sampling methods. We plan to use these absorption techniques to measure RSV viral load. We also aim to look at the immune response in terms of the anti-viral interferon response (IFN-γ, IFN-λ, IFN-α2a, IP10, ITAC). In therapeutic studies in the future, it may be possible to document levels of drug (pharmacokinetics) in nasal MLF.

• Study Type: Interventional
• Enrollment (Actual): 152
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W2 1NY
    • Imperial College NHS Healthcare Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 weeks to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Group 1 and Group 2

Inclusion Criteria

• Infants aged 2 weeks-24 months
• Presentation to the Emergency Department with any upper respiratory tract infection (URTI) in the RSV season (Oct-March).

OR • Documented RSV infection, admitted to the paediatric wards at St Mary's Hospital.

Exclusion Criteria

• Any local or systemic factor that would influence the safety of nasal sampling.
• Bilateral indwelling nasal catheters or local nasal pathology preventing access for nasal sampling.
• Bleeding disorders.
• The baby is taking part in another interventional study.
• The parents or guardians not able to sign the informed consent from due to limited English or comprehension despite the use of independent interpreter services.
• Limited life expectancy of the baby,

Group 3

Inclusion criteria

• Hospitalised Infants admitted to the PICU at St. Mary's Hospital, aged 2 weeks-24 months with documented RSV infection (by rapid test and/or PCR).
• Infants of weight >2kg.
• On a conventional ventilator with an Endotracheal Tube (ETT) of >3.0mmm diameter

Exclusion criteria

• Any local or systemic factor that would influence the safety of nasal sampling.
• Bilateral nasal catheters or local nasal pathology preventing access for nasal sampling.
• The baby is taking part in another interventional study.
• Prematurity - corrected gestational age <36 weeks, weight <2kg
• Significant hypoxia or instability precluding ventilator disconnection
• ETT < 3mm internal diameter
• Transcutaneous oxygen saturation of <95% on 60% oxygen
• Risk of bleeding
• Pneumothorax
• Infants receiving oral corticosteroid therapy at any time in past month
• Parents or guardians not able to sign informed consent from due to limited English or understanding despite the use of independent interpreter services.
• Limited life expectancy or a decision to limit management,

Control Group 1 Inclusion criteria

• Babies, aged 2 weeks-24 months, attending routine outpatient appointments or undergoing elective surgical procedures.

Exclusion criteria

• Any respiratory symptoms
• All other exclusion are the same as Groups 1 and 2

Control Group 2

Inclusion criteria

• Infants aged 2 weeks-24 months.
• Infants ventilated on the PICU for any condition
• Confirmed RSV negative by PCR of respiratory tract samples

Exclusion Criteria

• All exclusions are the same as Group 3
• In addition - any concern about raised intracranial pressure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Emergency Department; Babies with suspected respiratory tract infection (RTI) in the ED	Diagnostic test: Nasal and Bronchial Sampling; Nasal Absorption sampling, Bronchial sampling, Nasal Pharageal Aspirates, Blood sampling.
Other: Paediatric Wards; Babies with diagnosed RSV infection admitted to paediatric wards	Diagnostic test: Nasal and Bronchial Sampling; Nasal Absorption sampling, Bronchial sampling, Nasal Pharageal Aspirates, Blood sampling.
Other: Paediatric Intensive Care; Babies with diagnosed severe RSV infection in PICU requiring mechanical ventilation	Diagnostic test: Nasal and Bronchial Sampling; Nasal Absorption sampling, Bronchial sampling, Nasal Pharageal Aspirates, Blood sampling.
Other: Health Controls; Babies without respiratory symptoms, attending routine outpatient appointments or undergoing elective surgical procedures	Diagnostic test: Nasal and Bronchial Sampling; Nasal Absorption sampling, Bronchial sampling, Nasal Pharageal Aspirates, Blood sampling.
Other: Controls in Paediatric Intensive Care; Babies without RSV infection but requiring mechanical ventilation in PICU	Diagnostic test: Nasal and Bronchial Sampling; Nasal Absorption sampling, Bronchial sampling, Nasal Pharageal Aspirates, Blood sampling.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Sampling Visits on Which Participants Are Willing to Undergo Nasosorption and/or NPA Sampling	To determine the difference in tolerability of nasosorption compared to NPA by assessment of acceptance by infants and families. Samples were collected from participants up to twice daily throughout study involvement, as such each participant could have >1 sampling visits.	Throughout symptomatic respiratory infection, up to 1 month
Accuracy of Nasosorption for Viral Load Measurement	To determine the difference in accuracy of nasosorption compared to NPA by assessment of level of viral load (measured by qPCR).	Throughout symptomatic respiratory infection, up to 1 month
Accuracy of Bronchosorption for Viral Load Measurement, Compared to Tracheal Aspirate	To determine the difference in accuracy of bronchosorption (BSAM) compared to tracheal aspirate (TA) by assessment of level of viral load (measured by qPCR).	Throughout symptomatic respiratory infection, up to 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune Response	Establishing the use of nasal and bronchial sampling to measure the host immune response to RSV. We will determine cytokine and inflammatory mediator concentrations by immunoassay of eluted fluid from nasosorption and compare with NPA.	Throughout symptomatic respiratory infection, up to 1 month

Collaborators and Investigators

• Sponsor: Imperial College Healthcare NHS Trust
• Collaborators: Pulmocide Ltd

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2015
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): June 30, 2018

Study Registration Dates

• First Submitted: February 7, 2017
• First Submitted That Met QC Criteria: February 20, 2017
• First Posted (Actual): February 24, 2017

Study Record Updates

• Last Update Posted (Actual): November 12, 2019
• Last Update Submitted That Met QC Criteria: October 22, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Bronchial Diseases; Paramyxoviridae Infections; Mononegavirales Infections; Lung Diseases, Obstructive; Pneumovirus Infections; Bronchitis; Respiratory Insufficiency; Respiratory Syncytial Virus Infections; Bronchiolitis; Bronchiolitis, Viral
• Other Study ID Numbers: 15/WM/0343

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Participants consented that blood or nasal samples taken during this study can be used in the future for any ethically-approved studies.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No