Pediatric Intensive Care Ulcer Prophylaxis Pilot Trial

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Pediatric Intensive Care Ulcer Prophylaxis Pilot Trial

Conditions
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Gastrointestinal Hemorrhage

Intervention / Treatment
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* Drug: Pantoprazole
* Drug: Placebo (for pantoprazole)


Participation Criteria
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Eligibility Criteria
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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 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

Ages Eligible for Study
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Minimum Age: 4 Months
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pantoprazole<br>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<br> <br> |
| Placebo Comparator: placebo (for pantoprazole)<br>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)<br> <br> |

What is the study measuring?
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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) |