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19/73 The use of mucoactive agents for patients with acute respiratory failure in critical care




The aim of the HTA Programme is to ensure that high quality research information on the effectiveness, costs and broader impact of health technology is produced in the most efficient way for those who use, manage, provide care in or develop policy for the NHS. Topics for research are identified and prioritised to meet the needs of the NHS. Health technology assessment forms a substantial portfolio of work within the National Institute for Health Research and each year about fifty new studies are commissioned to help answer questions of direct importance to the NHS. The studies include both primary research and evidence synthesis.

Research Question: Does the use of inhaled or systemic mucoactives in mechanically ventilated patients with acute respiratory failure improve patient outcomes?

  1. Interventions: Inhaled and/or systemic mucoactives such as carbocysteine, N-acetylcysteine and hypertonic saline in addition to usual care (and other management). Applicants to define and justify the choice of intervention(s), dose and regimens to test, or not, and in which combinations.
  2. Patient group: Adult critical care patients receiving mechanical ventilation for treatment of acute respiratory failure (applicants to define and justify).
    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: Critical care.
  4. Control: Usual care not including mucoactives, to be defined and justified by applicants. Other management, including the use of airway clearance techniques/physiotherapy and nebulised isotonic saline should be the same in treatment and control groups.
  5. Study design: A randomised study including an internal pilot phase to test the ability to recruit and randomise. Clear stop/go criteria should be provided to inform progression from pilot to full trial.  Applicants should explain how their choice of primary outcome will mitigate the risk of bias.
  6. Important outcomes: Length of critical care and hospital stay; duration of ventilation; mortality; need for re-intubation; adverse events.
    Other outcomes: Antibiotic usage; other patient reported outcomes; frequency of manual airway clearance; cost-effectiveness.
  7. Minimum duration of follow-up: 60 days.
    Longer-term follow up: If appropriate, researchers should consider obtaining consent from participants to allow potential future follow up through efficient means (such as routine data) as part of a separately funded study.


Acute respiratory failure (ARF) is a frequent cause of admission to critical care and can be a medical emergency with significant mortality. Patients often require invasive mechanical ventilation as part of critical care management which can be complicated by airway secretions. How best to manage these problematic secretions, which can block the airways, remains a clinical quandary with no good quality evidence on which to base practice.

While respiratory physiotherapy has an important role to play a variety of both systemic and topical/nebulised mucoactive agents are in common use, which aim to loosen or minimise secretions in order to maintain or improve airway patency. Evidence of effectiveness about these various agents (isotonic and hypertonic saline, N-acetylcysteine and carbocysteine) is almost non-existent but they are still widely used in practice, almost always based on personal clinical opinion following clinical observation (because there are no established indication criteria or guidelines to follow).

The critical care community have highlighted their concerns about the lack of guidance and evidence and have indicated the importance of further research in this area.

The HTA programme therefore seeks applications which address the uncertainties about the clinical and cost-effectiveness of mucoactive agent use for ventilated patients with ARF in critical care.

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 wish to submit a Stage 1 application for this call, the online application form can be found on the Funding opportunities page.  To select this call, use the filters on the right of the screen or search using the call name and/or number.

Your application must be submitted on-line no later than 1pm on the 25th September 2019. Applications will be considered by the HTA Funding Committee at its meeting in November.

Guidance notes and supporting information for HTA Programme applications are available by clicking the links.

IMPORTANT: Shortlisted Stage 1 applicants will be given eight weeks to submit a Stage 2 application. The Stage 2 application will be considered at the Funding Committee in March.

Applications received after 1300 hours on the due date will not be considered.

Should you have any queries please contact us:


Telephone: General Funding Committee 02380 595630