Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease

NCT03667703 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: IRB-P00028715
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Infants with congenital heart disease often require an intervention during their first year of life. Infants are generally admitted to a cardiac intensive care unit and are routinely prescribed stress ulcer prophylaxis to decrease acid release from the stomach to prevent stress ulcer formation. However, these medicines may not be safe and could put infants at increased risk for hospital-acquired infections, necrotizing enterocolitis and alteration to the infant's microbiome. The investigators plan to assess the feasibility of conducting a prospective, blinded randomized control trial to determine the safety of withholding stress ulcer prophylaxis in critically ill infants with congenital heart disease. In addition, the investigators plan to examine the changes to the infant's microbiome through oral, gastric and stool samples and compare hospital-acquired infections.

Conditions

Congenital Heart Disease; Upper Gastrointestinal Bleeding; Stress Ulcer; Infection

Outcome Measures

Primary Outcomes (2)

• Predefined Feasibility Outcomes to Assess Trial Success

  Feasibility will be defined by the following metrics: (1) if \>80% of eligible patients are approached for consent (screening), (2) \>20% of eligible patients are randomized (consent and enrollment), (3) \>80% of enrolled patients received first dose of study drug within 48 hours (allocation), and (4) \>80% compliance to protocol and treatment group (protocol adherence).

  Through study completion, anticipated 2 years.

• Rate of upper gastrointestinal bleeds

  To examine the difference in the incidence of clinically significant upper gastrointestinal (UGI) bleeding in critically ill infants with CHD receiving SUP versus placebo to demonstrate safety.

  Through study completion, anticipated 2 years.

Secondary Outcomes (2)

• Microbiome alterations

  Through study completion, anticipated 2 years.

• Rate of hospital-acquired infections

  Through study completion, anticipated 2 years.

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Subjects randomized to placebo will receive an equivalent volume (mL) of normal saline intravenously or Ora-plus orally based on weight and age.

Drug: Placebo

Study Drug

ACTIVE COMPARATOR

Subjects randomized to study drug will receive famotidine, a histamine-2 receptor antagonist. Dosing will be weight based and age-dependent. Infants \< 90 days old will receive either 0.5mg/kg intravenously daily or 0.5mg/kg orally twice a day of famotidine. Infants ≥ 90 days or older will receive 0.25mg/kg intravenously every 12 hours or 0.5mg/kg orally twice a day.

Drug: Famotidine

Interventions

Famotidine DRUG

Patients will be randomized to either receive a placebo or famotidine (study drug).

Also known as: Pepcid

Study Drug

Placebo DRUG

Patients will be randomized to either receive a placebo or famotidine (study drug).

Also known as: Normal saline or stevoside-free syrup

Placebo

Eligibility Criteria

• Age: 1 Minute - 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \< 12 months of age (including premature newborns),
• diagnosed with congenital heart disease (including anatomic, myopathic and arrhythmic conditions),
• received ≤ 1 dose of SUP (including histamine-2 receptor antagonists, proton pump inhibitors, and sucralfate) during current admission, AND
• anticipated to require respiratory support for \> 24 hours during their CICU stay. Respiratory support includes mechanical ventilation, non-invasive positive-pressure ventilation and high-flow oxygen therapy.

You may not qualify if:

• prior use of antacids (including histamine-2 receptor antagonists, proton pump inhibitors, or sucralfate) in the past month for \> 7 days,
• active gastrointestinal bleeding,
• active Helicobacter pylori infection,
• administration of high-dose steroids (equivalent dosing to 15 mg/kg/day of methylprednisolone),
• will receive ketorolac (intravenous nonsteroidal anti-inflammatory drug) during admission,
• exposed to specific anticoagulants (high-dose aspirin, direct thrombin inhibitors and GPIIbIIIa inhibitors),
• planned to undergo or recently has undergone gastrointestinal surgery (i.e. repair of duodenal atresia)
• supported by extracorporeal membrane oxygenator (ECMO) or ventricular assist device (VAD),
• currently enrolled in another intervention trial,
• known to be allergic to H2RAs,
• admitted for palliative care,
• prior enrollment in the study, OR
• primary provider declines enrollment.

Sponsors & Collaborators

• Boston Children's Hospital: lead
• The Gerber Foundation: collaborator

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (2)

• Mills KI, Albert BD, Bechard LJ, Chu S, Duggan CP, Kaza A, Rakoff-Nahoum S, Sleeper LA, Newburger JW, Priebe GP, Mehta NM. Stress Ulcer Prophylaxis Versus Placebo-A Blinded Pilot Randomized Controlled Trial to Evaluate the Safety of Two Strategies in Critically Ill Infants With Congenital Heart Disease. Pediatr Crit Care Med. 2024 Feb 1;25(2):118-127. doi: 10.1097/PCC.0000000000003384. Epub 2024 Jan 19.

  PMID: 38240536 DERIVED

• Mills KI, Albert BD, Bechard LJ, Duggan CP, Kaza A, Rakoff-Nahoum S, Vlamakis H, Sleeper LA, Newburger JW, Priebe GP, Mehta NM. Stress ulcer prophylaxis versus placebo-a blinded randomized control trial to evaluate the safety of two strategies in critically ill infants with congenital heart disease (SUPPRESS-CHD). Trials. 2020 Jun 29;21(1):590. doi: 10.1186/s13063-020-04513-w.

  PMID: 32600393 DERIVED

MeSH Terms

Conditions

Heart Defects, Congenital; Gastrointestinal Hemorrhage; Duodenal Ulcer; Infections

Interventions

Famotidine; Saline Solution

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Gastrointestinal Diseases; Digestive System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Peptic Ulcer; Duodenal Diseases; Intestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Kimberly I Mills, MD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

• Ben D Albert, MD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

• Nilesh M Mehta, MD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant in Cardiology, Instructor in Pediatrics

Model Details: Prospective, double-blinded randomized placebo-controlled pilot feasibility trial

Study Record Dates

• First Submitted: July 13, 2018
• First Posted: September 12, 2018
• Study Start: March 10, 2019
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2022
• Last Updated: September 21, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)