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19/126 Suspending proton pump inhibitors to reduce Clostridium




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 stopping proton pump inhibitors during a course of antibiotics reduce the rate of Clostridium difficile infection for patients in hospital?

  1.  Intervention: Suspension of proton pump inhibitors during a course of antibiotics – to be defined by applicants.
  2.  Patient group:  Adults (including older adults) in hospital prescribed an acute course of antibiotics who are already taking proton pump inhibitors – exact inclusion criteria to be defined and justified by applicants.
    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: Hospital.
  4. Comparator: Continued use of proton pump inhibitors during a course of antibiotics.
  5. Study design: A pragmatic randomised controlled trial with 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.
  6. Important outcomes: Measures of Clostridium difficile infection including incidence/recurrence.
    Other outcomes: Gastrointestinal symptoms; length of hospital stay; morbidity/mortality; adverse effects associated with suspension of PPIs; cost-effectiveness.
  7. Minimum duration of follow-up: To be defined and justified by applicants.
    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.


Infection with Clostridium difficile bacterium remains an unpleasant, and potentially severe or fatal infection, especially in the elderly and other vulnerable patient groups. It is recognised as an avoidable cause of mortality and morbidity, especially amongst patients in hospital, and has a significant impact on health services in terms of cost and hospital beds occupied. Whilst the NHS has made great strides in reducing the numbers of Clostridium difficile infections (CDIs), the rate of improvement has slowed and become approximately stable in recent years.

Antibiotics, hospitalisation and older age are all risk factors known to be associated with an increased incidence of CDI. In addition, the current weight of evidence indicates a clinical association between proton pump inhibitor (PPI) use and CDI. PPIs are among the most frequently prescribed drugs globally. They reduce acid secretion and are used for treating many conditions such as gastroesophageal reflux disease and dyspepsia. Many people remain on PPIs for much longer than required. Systematic reviews of retrospective observational data have concluded that the use of PPIs together with antibiotics may be associated with a significantly higher incidence of CDI compared to either alone. Such findings have been used to support the judicious use of PPIs for the prevention of CDI. For example, Public Health England suggests that consideration should be given to stopping/reviewing the need for PPIs in patients with or at high risk of CDI.

In recent years there has been a change in practice in some hospitals to suspend PPIs during a course of antibiotics, in order to reduce the risk of CDI. However, this practice varies between Trusts and between clinicians. For some clinicians there is concern of re-bleed from previous peptic ulceration, particularly in the acutely unwell patient. There is clinical equipoise over the practice, little high quality evidence to support it, and the balance of benefits and harms are not known. As such, the HTA Programme is interested in commissioning the research outlined above.

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 1st April 2020. Applications will be considered by the HTA Funding Committee at its meeting in May 2020.

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 September 2020.

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

Should you have any queries please contact us:


Commissioning Funding Committee 02380 595510