Biomarker-based Exclusion of VAP for Improved Antibiotic Stewardship

NCT01972425 | Completed DMC

• 2 other identifiers: NUTH629365937227
• Study Type: interventional
• Target: 211
• Locations: 1 country
• Sites: 19

Brief Summary

Critically ill patients whose lungs are supported by breathing machines (ventilators) commonly develop a new lung infection, called ventilator-associated pneumonia (VAP). Because VAP is often fatal, antibiotics are administered whenever it is suspected. However VAP is hard to distinguish from several non-infective lung conditions and most patients with suspected VAP do not have pneumonia. Therefore many patients receive unnecessary antibiotics for several days, promoting emergence of 'superbugs'. Laboratory test results for diagnosing VAP typically only reach the doctors after 3 days. A simple test rapidly and confidently excluding VAP should improve patient care, reduce unnecessary antibiotics and decrease costs. We recently showed that low levels of specific proteins in fluid from the lungs of patients with suspected VAP effectively excluded VAP, using a test that may yield results within 6 hours. The test used is an extension of existing technology produced by our commercial partner Becton Dickinson (BD) Biosciences. Our previous findings were derived from a single hospital's intensive care unit. We have recently confirmed this finding across many intensive care units, which will help show that the test can be used in 'real life'. The aim of this study is to take the new test to the next step and determine whether it can improve the care of patients by reducing the amount of unnecessary antibiotics prescribed. This will be done using a 'randomised controlled trial', the best tool for scientifically testing a new diagnostic test. To do this we shall identify patients with suspected VAP, all of whom will have a lung sample - half of the patients will receive 'usual care' for suspected VAP, the other half will have the new test performed on their lung fluid. If the new test suggests no lung infection, the doctors will be asked to consider not giving antibiotics. We shall test how much antibiotic is given to each group.

Conditions

Ventilator-associated Pneumonia

Outcome Measures

Primary Outcomes (1)

• Antibiotic free days (AFD)

  The frequency distribution of antibiotic-free days (AFD) in the 7 days following BAL

  7 days

Study Arms (2)

Biomarker-based diagnostic

EXPERIMENTAL

Analyse sample on arrival

Other: Biomarker-based diagnostic

Routine use of antibiotics

NO INTERVENTION

Do not analyse the sample on arrival

Interventions

Biomarker-based diagnostic OTHER

The intervention will be a biomarker-based diagnostic test for the exclusion of VAP

Biomarker-based diagnostic

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Mechanically ventilated for ≥ 48hrs
• or more of:
• Temperature \<35ºC or \>38ºC
• White cell count \<4x109/L or \>11x109/L
• Purulent tracheal secretions
• New or worsening CXR or CT scan changes
• The patient is considered suitable for early discontinuation of antibiotics

You may not qualify if:

• PaO2\<8kPa on FiO2\>0.7
• Positive end-expiratory pressure \>15cmH2O
• Peak airway pressure \>35 cmH2O
• Heart rate \>140 bpm
• Mean arterial pressure \<65mmHg
• Bleeding diathesis (including platelet count \<20x109 per litre of blood or international normalised ratio (INR) \>3)
• Poorly controlled intracranial pressure (\>20mmHg)
• ICU consultant deems procedure not to be safe
• Previous BAL as part of this study
• Consent declined
• Patients who are enrolled in observational studies will be eligible for co-enrolment. Co-enrolment with interventional studies will be possible following consideration of any scientific or statistical interaction, in accordance with current UK critical care research forum (UKCCRF) recommendations (see appendix). Until co-enrolment is considered appropriate for a particular study, patients enrolled in an interventional trial will not be included.

Sponsors & Collaborators

• Newcastle-upon-Tyne Hospitals NHS Trust: lead
• Wellcome Trust: collaborator

Study Sites (19)

Royal Victoria Hospital

Belfast, County Antrim, BT12 6BA, United Kingdom

Location

Wansbeck General Hospital

Ashington, Tyne and Wear, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, Tyne and Wear, NE7 7DN, United Kingdom

Location

Sunderland Royal Hospital

Sunderland, Tyne and Wear, SR4 7TP, United Kingdom

Location

Birmingham Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

Location

Sandwell and West Birmingham

Birmingham, United Kingdom

Location

Countess of Chester Hospital

Chester, CH2 1UL, United Kingdom

Location

University Hospital Coventry

Coventry, CV4 7AL, United Kingdom

Location

Russells Hall Hospital

Dudley, United Kingdom

Location

Edinburgh Royal Infirmary

Edinburgh, EH16 4TS, United Kingdom

Location

Western General Hospital

Edinburgh, United Kingdom

Location

Queen Elizabeth Hospital

Gateshead, United Kingdom

Location

Royal Liverpool Hospital

Liverpool, United Kingdom

Location

Chelsea and Westminster Hospital

London, SW10 9NH, United Kingdom

Location

Manchester Royal Infirmary

Manchester, United Kingdom

Location

James Cook University Hospital

Middlesbrough, United Kingdom

Location

North Tyneside General Hospital

North Shields, NE29 8NH, United Kingdom

Location

Royal Preston Hospital

Preston, PR2 9HT, United Kingdom

Location

Salford Royal Hospital

Salford, M6 8HD, United Kingdom

Location

Related Publications (3)

• Hellyer TP, McAuley DF, Walsh TS, Anderson N, Conway Morris A, Singh S, Dark P, Roy AI, Perkins GD, McMullan R, Emerson LM, Blackwood B, Wright SE, Kefala K, O'Kane CM, Baudouin SV, Paterson RL, Rostron AJ, Agus A, Bannard-Smith J, Robin NM, Welters ID, Bassford C, Yates B, Spencer C, Laha SK, Hulme J, Bonner S, Linnett V, Sonksen J, Van Den Broeck T, Boschman G, Keenan DJ, Scott J, Allen AJ, Phair G, Parker J, Bowett SA, Simpson AJ. Biomarker-guided antibiotic stewardship in suspected ventilator-associated pneumonia (VAPrapid2): a randomised controlled trial and process evaluation. Lancet Respir Med. 2020 Feb;8(2):182-191. doi: 10.1016/S2213-2600(19)30367-4. Epub 2019 Dec 3.

  PMID: 31810865 DERIVED

• Conway Morris A, Gadsby N, McKenna JP, Hellyer TP, Dark P, Singh S, Walsh TS, McAuley DF, Templeton K, Simpson AJ, McMullan R. 16S pan-bacterial PCR can accurately identify patients with ventilator-associated pneumonia. Thorax. 2017 Nov;72(11):1046-1048. doi: 10.1136/thoraxjnl-2016-209065. Epub 2016 Dec 14.

  PMID: 27974525 DERIVED

• Hellyer TP, Anderson NH, Parker J, Dark P, Van Den Broeck T, Singh S, McMullan R, Agus AM, Emerson LM, Blackwood B, Gossain S, Walsh TS, Perkins GD, Conway Morris A, McAuley DF, Simpson AJ. Effectiveness of biomarker-based exclusion of ventilator-acquired pneumonia to reduce antibiotic use (VAPrapid-2): study protocol for a randomised controlled trial. Trials. 2016 Jul 16;17(1):318. doi: 10.1186/s13063-016-1442-x.

  PMID: 27422026 DERIVED

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• John Simpson

  Newcastle University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2013
• First Posted: October 30, 2013
• Study Start: October 1, 2013
• Primary Completion: September 1, 2016
• Study Completion: November 1, 2016
• Last Updated: March 28, 2017

Record last verified: 2017-03

Locations

GB (19)