PIC-UP: Pediatric Intensive Care Ulcer Prophylaxis Pilot Trial
Study Details
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 |
|---|---|---|
|
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
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
- Effective screening [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.
- Timely enrollment [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.
- Participant accrual [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.
- Protocol adherence [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
- Clinically important bleeding [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.
- Nosocomial infections [During admission to the Pediatric Intensive Care Unit (to maximum of 30 days)]
Ventilator associated pneumonia and C Difficile associated diarrhea
- Other gastrointestinal bleeding [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
Criteria
Inclusion Criteria:
-
less than 18 years of age
-
4 months of age
-
requires respiratory support in the form of invasive mechanical ventilation, non-invasive mechanical ventilation, or high-flow oxygen
-
the attending physician expects the child to require respiratory support for at least 2 more days
Exclusion Criteria:
-
histamine-2 receptor antagonist (H2RA) or proton pump inhibitor (PPI) use for >1 week in the past month
-
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.
-
documented severe reflux, active H. pylori infection, severe esophagitis, Zollinger Ellison syndrome, Barrett's esophagus, peptic ulcer bleeding within 8 weeks
-
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
-
are receiving mycophenolate (enteral), methotrexate, nelfinavir, atazanavir, saquinavir, posaconazole
-
chronic ventilation on usual pressure settings and rate
-
nocturnal or intermittent non-invasive ventilation only
-
are eating, nursing, or if chronically fed via feeding tube, receiving usual feeds
-
received more than 1 daily-dose equivalent of acid suppressive medication in the PICU
-
were previously enrolled in this trial
-
are currently enrolled in a potentially confounding trial
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are known to be pregnant or breastfeeding
-
are known to be allergic to pantoprazole or any other ingredient in the product
-
are not expected to survive this PICU admission because of palliative care or limited life support
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Alberta Children's Hospital | Calgary | Alberta | Canada | |
| 2 | IWK Health Centre | Halifax | Nova Scotia | Canada | |
| 3 | McMaster Children's Hospital | Hamilton | Ontario | Canada | L8N 3Z5 |
| 4 | Children's Hospital - London Health Science Centre | London | Ontario | Canada | N6A 5W9 |
| 5 | Children's Hospital of Eastern Ontario | Ottawa | Ontario | Canada | K1H 8L1 |
| 6 | CHU Sainte-Justine | Montreal | Quebec | Canada | |
| 7 | 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
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2173