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

• ClinicalTrials.gov Identifier: NCT02929563
• Recruitment Status: Completed
• First Posted: October 11, 2016
• Last Update Posted: September 2, 2020
• Sponsor: McMaster University
• Collaborator: Canadian Institutes of Health Research (CIHR)
• Information provided by (Responsible Party): McMaster University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Gastrointestinal Hemorrhage	Drug: Pantoprazole; Drug: Placebo (for pantoprazole)	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Pediatric Intensive Care Ulcer Prophylaxis Pilot Trial
• Actual Study Start Date: January 9, 2017
• Actual Primary Completion Date: January 2020
• Actual Study Completion Date: January 2020

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. Effective screening [ Time Frame: During admission to the Pediatric Intensive Care Unit (to maximum of 30 days) ]
   We will consider the trial feasible if >80% of eligible patients are approached for consent.
2. Timely enrollment [ Time Frame: During admission to the Pediatric Intensive Care Unit (to maximum of 30 days) ]
   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.
3. Participant accrual [ Time Frame: During admission to the Pediatric Intensive Care Unit (to maximum of 30 days) ]
   We will consider the trial feasible if the average monthly enrollment is 2 or more participants per centre.
4. Protocol adherence [ Time Frame: During admission to the Pediatric Intensive Care Unit (to maximum of 30 days) ]
   We will consider the trial feasible if >90% of doses are administered according to the protocol.

Secondary Outcome Measures :

1. Clinically important bleeding [ Time Frame: During admission to the Pediatric Intensive Care Unit (to maximum of 30 days) ]
   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.
2. Nosocomial infections [ Time Frame: During admission to the Pediatric Intensive Care Unit (to maximum of 30 days) ]
   Ventilator associated pneumonia and C Difficile associated diarrhea
3. Other gastrointestinal bleeding [ Time Frame: During admission to the Pediatric Intensive Care Unit (to maximum of 30 days) ]
   Bleeding from the gastrointestinal tract that is not clinically important (using the above criteria).

Eligibility Criteria

• Ages Eligible for Study: 4 Months to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Canada, Alberta

Alberta Children's Hospital

Calgary, Alberta, Canada

Canada, Nova Scotia

IWK Health Centre

Halifax, Nova Scotia, Canada

Canada, Ontario

McMaster Children's Hospital

Hamilton, Ontario, Canada, L8N 3Z5

Children's Hospital - London Health Science Centre

London, Ontario, Canada, N6A 5W9

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada, K1H 8L1

Canada, Quebec

CHU Sainte-Justine

Montreal, Quebec, Canada

Montreal Children's Hospital

Montréal, Quebec, Canada

Sponsors and Collaborators

McMaster University

Canadian Institutes of Health Research (CIHR)

Investigators

• Principal Investigator: Mark Duffett, PhD; McMaster University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: McMaster University
• ClinicalTrials.gov Identifier: NCT02929563
• Other Study ID Numbers: 2173
• First Posted: October 11, 2016
• Last Update Posted: September 2, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Additional relevant MeSH terms:

Gastrointestinal Hemorrhage; Hemorrhage; Pathologic Processes; Gastrointestinal Diseases; Digestive System Diseases; Pantoprazole; Anti-Ulcer Agents; Gastrointestinal Agents; Proton Pump Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action