Pediatric Intensive Care Ulcer Prophylaxis Pilot Trial (PIC-UP)

This study tests the feasibility of a large study of stress ulcer prophylaxis in critically ill children. Children admitted to the Pediatric Intensive Care Unit who are expected to require mechanical ventilation for more than 48 hours will be randomized to intravenous pantoprazole 1 mg/kg or matching placebo once daily until they no longer need mechanical ventilation.

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Hemorrhage
• Intervention / Treatment: Drug: Pantoprazole; Drug: Placebo (for pantoprazole)

Detailed Description

Despite sparse pediatric data on the effectiveness of stress ulcer prophylaxis to prevent gastrointestinal (GI) bleeding, 60% of critically ill children receive these medications. This may have unintended consequences - increasing the risk of nosocomial infections - which may be more serious and common than bleeding these drugs are prescribed to prevent. A large randomized trial (RCT) is needed to assess the balance of these risks and benefits, to determine if a strategy of withholding stress ulcer prophylaxis in critically ill children is not inferior to a strategy of routine stress ulcer prophylaxis. RCTs in pediatric critical care are exceptionally challenging to complete; thus, a rigorous pilot RCT is crucial. The pilot may prevent pursuit of a trial that is ultimately not feasible - which is ethically and financially responsible. It is more likely that this carefully designed pilot trial will ensure that the larger trial we undertake is successful.

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Alberta Children's Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • IWK Health Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster Children's Hospital
    • London, Ontario, Canada, N6A 5W9
      • Children's Hospital - London Health Science Centre
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
  • Quebec
    • Montreal, Quebec, Canada
      • CHU Sainte-Justine
    • Montréal, Quebec, Canada
      • Montreal Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. less than 18 years of age
2. >4 months of age
3. requires respiratory support in the form of invasive mechanical ventilation, non-invasive mechanical ventilation, or high-flow oxygen
4. the attending physician expects the child to require respiratory support for at least 2 more days

Exclusion Criteria:

1. histamine-2 receptor antagonist (H2RA) or proton pump inhibitor (PPI) use for >1 week in the past month
2. active GI bleeding Blood in the nasogastric (NG) tube or coffee-ground emesis suspected by the attending physician to be from the oropharynx is not an exclusion criterion.
3. documented severe reflux, active H. pylori infection, severe esophagitis, Zollinger Ellison syndrome, Barrett's esophagus, peptic ulcer bleeding within 8 weeks
4. are receiving methylprednisolone 15 mg/kg/day or more (or equivalent) Equivalent doses: methylprednisolone, prednisone or prednisolone 15 mg/kg/day; dexamethasone 3 mg/kg/day; hydrocortisone 60 mg/kg/day
5. are receiving mycophenolate (enteral), methotrexate, nelfinavir, atazanavir, saquinavir, posaconazole
6. chronic ventilation on usual pressure settings and rate
7. nocturnal or intermittent non-invasive ventilation only
8. are eating, nursing, or if chronically fed via feeding tube, receiving usual feeds
9. received more than 1 daily-dose equivalent of acid suppressive medication in the PICU
10. were previously enrolled in this trial
11. are currently enrolled in a potentially confounding trial
12. are known to be pregnant or breastfeeding
13. are known to be allergic to pantoprazole or any other ingredient in the product
14. are not expected to survive this PICU admission because of palliative care or limited life support

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: pantoprazole; pantoprazole 1 mg/kg (maximum 40 mg) IV once daily until the participants no longer need mechanical ventilation - to a maximum of 30 days or until Pediatric Intensive Care Unit (PICU) discharge.	Drug: Pantoprazole
Placebo Comparator: placebo (for pantoprazole); an equivalent volume of normal saline IV once daily until the participants no longer need mechanical ventilation - to a maximum of 30 days or until PICU discharge.	Drug: Placebo (for pantoprazole)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effective screening	We will consider the trial feasible if >80% of eligible patients are approached for consent.	During admission to the Pediatric Intensive Care Unit (to maximum of 30 days)
Timely enrollment	We will consider the trial feasible if >80% of participants receive their first dose of the assigned study drug within 1 day of becoming eligible.	During admission to the Pediatric Intensive Care Unit (to maximum of 30 days)
Participant accrual	We will consider the trial feasible if the average monthly enrollment is 2 or more participants per centre.	During admission to the Pediatric Intensive Care Unit (to maximum of 30 days)
Protocol adherence	We will consider the trial feasible if >90% of doses are administered according to the protocol.	During admission to the Pediatric Intensive Care Unit (to maximum of 30 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically important bleeding	Overt bleeding from the GI tract (can be hematemesis, nasogastric blood, melena, hematochezia) associated with one of the following within 24 hours: a decrease in hemoglobin of >20 g/L, hypotension (a decrease in systolic blood pressure of >10 mmHg or the need for new or increased doses of vasoactive medications), tachycardia (an increase in heart rate of >20 beats per minute) or a red blood cell transfusion.	During admission to the Pediatric Intensive Care Unit (to maximum of 30 days)
Nosocomial infections	Ventilator associated pneumonia and C Difficile associated diarrhea	During admission to the Pediatric Intensive Care Unit (to maximum of 30 days)
Other gastrointestinal bleeding	Bleeding from the gastrointestinal tract that is not clinically important (using the above criteria).	During admission to the Pediatric Intensive Care Unit (to maximum of 30 days)

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Mark Duffett, PhD, McMaster University

Publications and helpful links

General Publications

• Duffett M, Choong K, Foster J, Gilfoyle E, Lacroix J, Pai N, Thabane L, Cook DJ; Canadian Critical Care Trials Group. Pediatric intensive care stress ulcer prevention (PIC-UP): a protocol for a pilot randomized trial. Pilot Feasibility Stud. 2017 May 19;3:26. doi: 10.1186/s40814-017-0142-y. eCollection 2017. Erratum In: Pilot Feasibility Stud. 2017 Aug 18;3:33.

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2017
• Primary Completion (Actual): January 1, 2020
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: October 3, 2016
• First Submitted That Met QC Criteria: October 7, 2016
• First Posted (Estimate): October 11, 2016

Study Record Updates

• Last Update Posted (Actual): September 2, 2020
• Last Update Submitted That Met QC Criteria: September 1, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Hemorrhage; Gastrointestinal Hemorrhage; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Pantoprazole
• Other Study ID Numbers: 2173

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided