Re-Evaluating the Inhibition of Stress Erosions: Gastrointestinal Bleeding Prophylaxis In ICU

NCT ID: NCT02290327

Last Updated: 2016-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 91 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31

Brief Summary

The purpose of the this Pilot Trial is to determine the feasibility of conducting a large randomized controlled trial (RCT), that aims to examine the efficacy and safety of using pantoprazole compared to placebo for stress ulcer prophylaxis in critically ill mechanically ventilated patients in the ICU.

Detailed Description

Background For almost 4 decades, stress ulcer prophylaxis to prevent upper gastrointestinal (GI) bleeding has been standard of care in the ICU. The 1999 American Society of Health-System Pharmacists guidelines recommend stress ulcer prophylaxis for the critically ill. The 2013 Surviving Sepsis Campaign guidelines recommend stress ulcer prophylaxis for patients mechanically ventilated for > 48 hours or with coagulopathy. However, GI bleeding rates are significantly lower today than in the past, potentially reduced by optimal resuscitation and early enteral nutrition. Additional concerns include whether acid suppression has any impact on bleeding at all, and whether acid suppression does more harm than good, given the apparent increased risk of more common, serious problems of pneumonia and Clostridium difficile infection. Further, prophylaxis has become almost universal rather than targetted at patients at risk of GI bleeding. Thus, clinicians and investigators globally are calling for a re-evaluation of acid suppression with a large Randomized controlled trial (RCT) comparing proton pump inhibitor against placebo.

Objectives To determine the feasibility of performing a large RCT to investigate whether intravenously administered pantoprazole, compared to placebo prevents clinically important gastrointestinal bleeding in mechanically ventilated patients in the intensive care unit (ICU), based on 3 outcomes: the informed consent rate; recruitment rate, and protocol adherence

Design Prospective, concealed, stratified, randomized, blinded, multicentre trial.

Setting Canadian and Saudi medical-surgical university-affiliated ICUs.

Methods Patients will be stratified by center, and medical/surgical/trauma status, then will be randomized to intervention or placebo using an allocation ratio of 1:1 and undisclosed variable block sizes. Research pharmacists will prepare identical 100ml mini-bags of the pantoprazole 40mg or placebo with blinded research labels for once daily dosing.

Followup Research Coordinators in the ICU will review all patients daily, where most of the trial data will be collected. This will involve baseline data (e.g., demographics, illness severity, advanced life support), and daily data (e.g., study medication administered and reasons why not administered), other relevant medications and co-interventions that might influence bleeding, ventilator associated pneumonia (VAP) or Clostridium difficile outcomes (e.g., enteral nutrition, antibiotics, anticoagulants, possible VAP prevention strategies including probiotics), laboratory, microbiology, transfusion or radiology documentation to help adjudicate the outcomes of clinically important and overt bleeding, VAP, and Clostridium difficile infection, and mortality. We do not anticipate any loss to follow up; we expect to have complete follow up of patients in the ICU.

Patients will be followed for primary and secondary outcomes during their ICU stay on daily basis. Once patients are discharged from the ICU, they will no longer be followed daily; only duration of hospital stay and vital status at hospital discharge will be obtained.

A secure web-based central randomization method will ensure site-specific stratified allocation tables. When the patient is identified as eligible and consent is obtained by Research Coordinator, the Research Pharmacist will take the assignment and dispense study drug accordingly.

Relevance Results of the REVISE Pilot Trial will provide key feasibility and safety data which will serve to plan a larger multicentre trial of pantoprazole versus placebo for stress ulcer prophylaxis in mechanically ventilated critically ill patients.

Conditions

Stress Ulcer Prophylaxis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

50 ml of 0.9% Normal Saline Intravenously once daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

50 ml of 0.9% normal saline

Pantoprazole

Pantoprazole 40 mg in 50 ml 0.9% Normal Saline Intravenously once daily

Group Type: ACTIVE_COMPARATOR

Pantoprazole

Intervention Type: DRUG

Proton pump inhibitor

Interventions

Pantoprazole

Proton pump inhibitor

Intervention Type: DRUG

Placebo

50 ml of 0.9% normal saline

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Adults ≥ 18 years

2. Anticipated invasive mechanical ventilation of ≥48 hours, determined by the intensivist

Exclusion Criteria

1. Invasive mechanical ventilation >72 hours before randomization.

2. Patients who must receive PPI due to active bleeding or increased bleeding risk (e.g., patients with acute GI bleeding, recent severe esophagitis, Zollinger Ellison syndrome, Barrett's esophagus, peptic ulcer bleeding within 8 weeks [mild dyspepsia or mild gastroesophageal reflex disease will not be excluded])

3. Receiving dual antiplatelet therapy aspirin and clopidogrel prior to randomization

4. Palliative care or decision to withdraw advanced life support (patients with a decision to forgo cardiopulmonary resuscitation will not be excluded)

5. Previous enrolment in this or a related trial

6. Pregnancy

7. Physician, patient, or substitute decision maker (SDM) declines

8. Two or more 'daily doses' of prophylaxis with H2RA or PPI (one day of a single PPI dose is not an exclusion criterion if once daily dosing of PPI prophylaxis was administered; one day of bid [twice daily] dosing of an H2RA is not an exclusion criterion if twice daily H2RA prophylaxis was administered; one day of tid [thrice daily] dosing of an H2RA is not an exclusion criterion if thrice daily H2RA prophylaxis was administered).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Physicians' Services Incorporated Foundation

OTHER

Sponsor Role: collaborator

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Waleed Alhazzani, MD,FRCPC,MSc

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Locations

Royal Adelaide

Adelaide, , Australia

Queen Elizabeth II

Halifax, Nova Scotia, Canada

St. Joseph's HealthCare Hospital

Hamilton, Ontario, Canada

Jurvinski Hospital

Hamilton, Ontario, Canada

Kingston General Hospital

Kingston, Ontario, Canada

Ottawa Civic Hospital

Ottawa, Ontario, Canada

Ottawa General Hospital

Ottawa, Ontario, Canada

Mount Sinai Hospital

Toronto, Ontario, Canada

St Michael's Hospital

Toronto, Ontario, Canada

Dammam University

Dammam, Eastern Province, Saudi Arabia

Countries

Australia; Canada; Saudi Arabia

References

Alhazzani W, Guyatt G, Marshall JC, Hall R, Muscedere J, Lauzier F, Thabane L, Alshahrani M, English SW, Arabi YM, Deane AM, Karachi T, Rochwerg B, Finfer S, Daneman N, Zytaruk N, Heel-Ansdell D, Cook D, Of OB. Re-evaluating the Inhibition of Stress Erosions (REVISE): a protocol for pilot randomized controlled trial. Ann Saudi Med. 2016 Nov-Dec;36(6):427-433. doi: 10.5144/0256-4947.2016.427.

Reference Type: DERIVED

PMID: 27920416 (View on PubMed)

Other Identifiers

REV-06MAR14

Identifier Type: -

Identifier Source: org_study_id