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23/156 Prophylactic nebulised antibiotics for patients with a permanent tracheostomy or who have undergone a laryngectomy commissioning brief


Published: 30 November 2023

Version: 1.0 November 2023

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The aim of the HTA Programme is to ensure that high quality research information on the clinical effectiveness, cost-effectiveness and broader impact of healthcare treatments and tests are produced in the most efficient way for those who plan, provide or receive care from NHS and social care services. The commissioned workstream invites applications in response to calls for research on specific questions which have been identified and prioritised for their importance to the NHS, patients and social care.

Research question

What is the clinical and cost-effectiveness of nebulised antibiotics as prophylaxis against lower respiratory tract infection, in patients living with a permanent tracheostomy or who have undergone a laryngectomy?

  1. Intervention: Usual care, to be defined and justified by applicants, plus prophylactic nebulised antibiotic(s). Applicants to define and justify the choice of antibiotic(s), as well as the dose and duration. 
  2. Patient group: Patients undergoing or having undergone a non-emergency tracheostomy or laryngectomy for any indication (applicants to define and justify, in particular with respect to the inclusion of children undergoing non-emergency tracheostomy), appropriately stratified based on age, underlying condition, time from tracheostomy or laryngectomy, frequency of lower respiratory tract infections, pre-tracheostomy/laryngectomy Pseudomonas colonisation (where culture results are available), and any other relevant parameters that might enable more precise guidelines on who is likely to benefit from prophylactic nebulised antibiotics and who is not (applicants to define and justify). This brief does not concern patients who have had a prolonged ICU stay and have yet to be weaned from a tracheostomy, but are not expected to live with it in the long term. Applications are encouraged which include recruitment from geographic populations with high disease burden which have been historically underserved by research activity in this field.
  3. Setting: Any appropriate setting.
  4. Comparator: Usual care, to be defined and justified by applicants, plus nebulised saline. Applicants may wish to consider a multi-arm trial, including a “usual care alone” arm.
  5. Study design: A randomised controlled trial with an internal pilot phase to test key trial processes, such as recruitment and adherence. Clear stop and go criteria should be provided to inform progression from pilot to full trial. Appropriate innovative trial designs are encouraged to identify the most optimal prophylactic regimen(s), in particular the timing, dose and duration, as well as criteria for selecting patients who are likely to benefit.
  6. Important outcomes: Exacerbation frequency (number of respiratory tract infections treated with antibiotics).
  7. Other outcomes: Time to first exacerbation; hospitalisation rates; number of antibiotic days; adverse effects; number of pneumonia events; suctioning events (where relevant); age-appropriate measures of health-related quality of life; breathlessness (BORG and MRCD scale – where relevant); patient and carer acceptability and ease of administration; Pseudomonas colonisation rate at 12 months; mortality; antimicrobial resistance; cost-effectiveness. Existing Core Outcomes should be included amongst the list of outcomes unless a good rationale is provided to do otherwise. Applicants are encouraged to report recruitment and findings disaggregated by sex (and other demographic factors where relevant).
  8. Minimum duration of follow-up: 12 months.
  9. Longer-term follow-up: If appropriate, researchers should consider obtaining consent to allow potential future follow-up through efficient means (such as routine data) as part of a separately funded study.


Tracheostomy and laryngectomy are procedures that result in the creation of alternative ways for air to access the lungs – the former by creating an opening in the trachea (windpipe), the latter by (permanently) removing the larynx. There are many different indications for these procedures and the patient group is diverse.

What most of these patients have in common is that they are increasingly able to live long and fulfilling lives with a tracheostomy tube or without a larynx, but with an increased risk of lower respiratory tract infections (LRTIs) following the procedure. Tracheostomy and laryngectomy make patients vulnerable to pathogens because natural defences offered by the upper airways are bypassed. In addition, many patients already carry harmful bacteria or acquire them in hospital, while their underlying condition, or a co-morbidity, might impair their ability to fight off an infection. LRTIs can lead to a deterioration of the patient’s condition, as well as significantly increase the cost of care.

There does not appear to be consensus among clinicians as to whether active prophylaxis aimed at preventing exacerbations should be pursued and, if so, what the most optimal prophylactic regime would look like. If effective, a therapy aimed at decreasing the frequency of exacerbations would improve the patients’ chances of survival and their quality of life, as well as driving down hospitalisation and other costs.

Antibiotics are available which are known to be effective against the bacteria most commonly associated with LRTIs in this patient group. They can be administered using a nebuliser which delivers them straight to the lungs, enabling a relatively large effect from a relatively small quantity, and limiting systemic adverse effects. Nebulised antibiotics are already recommended and widely used in treating chronic infections in cystic fibrosis and bronchiectasis. By contrast, there are currently no national guidelines for preventing LRTIs in patients who have undergone a tracheostomy or laryngectomy, and there appears to be a lack of consensus among clinicians around antibiotic prophylaxis.

Optimising the approach towards prevention of LRTIs in this patient group is also important in the context of antibiotic stewardship. Antibiotic prophylaxis may lead to the development of antimicrobial resistance. However, a well-targeted prophylaxis, with narrow-spectrum antibiotics whenever possible, could eliminate the need for broad-spectrum antibiotics further down the line.

The HTA Programme wishes to commission high-quality research to address the evidence gap in this area. As the patient group is very diverse, applications should set out how the heterogeneity will be managed, including defining appropriate stratification. Moreover, trial designs are encouraged that will make it possible to establish the criteria for deciding whether a particular patient was likely to benefit from prophylactic antibiotics and to optimise the timing, dosing and duration of the prophylaxis when it is offered.

For this question, mechanistic aspects of antimicrobial resistance are also of interest. Applicants who are successful in applying to this call are encouraged to consider applying to the MRC-NIHR Efficacy and Mechanism Evaluation (EME) programme to investigate the mechanism of action. The EME Researcher-Led funding opportunity is available to view separately. 

To support the ambitions of NIHR’s Best Research for Best Health: the next chapter, we strongly encourage the inclusion of nurses, midwives and allied health professionals within well-developed research teams responding to this call, to increase the building of research activity, capacity and capability across these professions.

Depending on the level of experience, this could be through the role of lead applicant, as joint co-applicant (supported by detailed mentoring plans submitted with the application), or as a co-applicant member of the research team. Through this activity, NIHR aims to support nurses, midwives and allied health professionals to become future research leaders and release the potential to lead, use, deliver and participate in research as a part of their job.

Additional commissioning brief background information

A background document is available that provides further information to support applicants for this call. It is intended to summarise what prompted the call and the existing evidence base, including relevant work from the HTA and wider NIHR research portfolio. It was researched and written on the basis of information from a search of relevant sources and databases, and in consultation with a number of experts in the field. If you would like a copy, please email

Making an application

If you would like to apply for this funding opportunity, you can begin your application via the funding opportunity page.

Your application must be submitted online no later than 1pm on 28 March 2024. Applications will be considered by the HTA Funding Committee at its meeting in May 2024.

Guidance notes and supporting information for HTA Programme applications are available.

Shortlisted Stage 1 applicants will be given 8 weeks to submit a Stage 2 application. The Stage 2 application will be considered at the Funding Committee in September 2024.

For commissioned topics, the Programme strongly discourages the practice of the same co-applicant joining more than one competing team, other than in unusual circumstances (for example, a lead from a named charity or a unique national expert in a condition).

For such exceptions, each application needs to state the case as to why the same person is included. The shared co-applicant should not divulge application details between teams, and both teams should acknowledge in their application that they are aware of the situation, and that study details have not been shared.

Should you have any queries please contact