See the published version of this preprint at Trials.
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Learn more about In Review
Study protocol
Nilesh Mehta
Boston Children's Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8146-2407
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Critically ill infants with congenital heart disease (CHD) are often prescribed stress ulcer prophylaxis (SUP) to prevent upper gastrointestinal bleeding, despite the low incidence of stress ulcers and limited data on the safety and efficacy of SUP in infants. Recently, SUP has been associated with an increased incidence of hospital-acquired infections, community-acquired pneumonia and necrotizing enterocolitis. The objective of this pilot study is to investigate the feasibility of performing a randomized controlled trial to assess the safety and efficacy of withholding SUP in infants with congenital heart disease admitted to the cardiac intensive care unit.
Methods: A single center, prospective, double-blinded, randomized placebo-controlled pilot feasibility trial will be performed in infants with CHD admitted to the cardiac intensive care unit and anticipated to require respiratory support for > 24 hours. Patients will be randomized to receive a histamine-2 receptor antagonist (H2RA) or placebo until they are discontinued from respiratory support. Randomization will be performed within 2 strata defined by admission type (medical or surgical) and age (neonate, age <30 days, or infant, 1 month to 1 year). Allocation will be a 1:1 ratio using permuted blocks to ensure balanced allocations across the two treatment groups within each stratum. The primary outcomes include feasibility of screening, consent, timely allocation of study drug, and protocol adherence. The primary safety outcome is the rate of clinically significant upper gastrointestinal bleeding. The secondary outcomes are the difference in the relative and absolute abundance of the gut microbiota and functional microbial profiles between the two study groups. We plan to enroll 100 patients in this pilot study.
Discussion: Routine use of SUP to prevent upper gastrointestinal bleeding in infants is controversial due to a low incidence of bleeding events and concern for adverse effects. The role of SUP in infants with CHD has not been examined and there is equipoise on the risks and benefits of withholding this therapy. In addition, this therapy has been discontinued in other neonatal populations due to the concern for hospital-acquired infections and necrotizing enterocolitis. Furthermore, exploring changes to the microbiome after exposure to SUP may highlight the mechanisms by which SUP impacts potential microbial dysbiosis of the gut and its association with hospital-acquired infections. Assessment of the feasibility of a trial of witholding SUP in critically ill infants with CHD will facilitate planning of a larger multicenter trial of safety and efficacy of SUP in this vulnerable population.
Trial registration: Clinicaltrials.gov; NCT03667703; submitted September 12, 2018
Keywords
pediatric critical care, pediatric cardiac critical care, pediatric intensive care, H2 blocker, congenital heart disease, gastrointestinal hemorrhage, infection, microbiome
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View the published article at Trials.
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Editorial decision: Accept
On 15 Jun, 2020
Reviewer #3 agreed
On 08 Jun, 2020
Reviewer #4 agreed
On 08 Jun, 2020
Review #2 received
Received 08 Jun, 2020
Review #3 received
Received 08 Jun, 2020
Review #1 received
Received 08 Jun, 2020
Review #4 received
Received 08 Jun, 2020
Reviewer #2 agreed
On 08 Jun, 2020
Reviewers invited
Invitations sent on 07 Jun, 2020
Reviewer #1 agreed
On 07 Jun, 2020
Editor assigned
On 26 May, 2020
Submission checks complete
On 25 May, 2020
No comments provided
Editorial decision: Minor revision
On 02 May, 2020
Review #4 received
Received 03 Apr, 2020
Review #3 received
Received 23 Mar, 2020
Review #2 received
Received 21 Mar, 2020
Review #1 received
Received 14 Mar, 2020
Reviewer #4 agreed
On 12 Mar, 2020
Reviewer #3 agreed
On 01 Mar, 2020
Reviewers invited
Invitations sent on 01 Mar, 2020
Reviewer #1 agreed
On 01 Mar, 2020
Reviewer #2 agreed
On 01 Mar, 2020
Editor assigned
On 21 Jan, 2020
Submission checks complete
On 16 Jan, 2020
First submitted
On 27 Dec, 2019
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See the published version of this preprint at Trials.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Study protocol
Nilesh Mehta
Boston Children's Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8146-2407
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Trials.
Version 2
Posted 03 Jun, 2020
No community comments so far
Editorial decision: Accept
On 15 Jun, 2020
Reviewer #3 agreed
On 08 Jun, 2020
Reviewer #4 agreed
On 08 Jun, 2020
Review #2 received
Received 08 Jun, 2020
Review #3 received
Received 08 Jun, 2020
Review #1 received
Received 08 Jun, 2020
Review #4 received
Received 08 Jun, 2020
Reviewer #2 agreed
On 08 Jun, 2020
Reviewers invited
Invitations sent on 07 Jun, 2020
Reviewer #1 agreed
On 07 Jun, 2020
Editor assigned
On 26 May, 2020
Submission checks complete
On 25 May, 2020
No comments provided
Editorial decision: Minor revision
On 02 May, 2020
Review #4 received
Received 03 Apr, 2020
Review #3 received
Received 23 Mar, 2020
Review #2 received
Received 21 Mar, 2020
Review #1 received
Received 14 Mar, 2020
Reviewer #4 agreed
On 12 Mar, 2020
Reviewer #3 agreed
On 01 Mar, 2020
Reviewers invited
Invitations sent on 01 Mar, 2020
Reviewer #1 agreed
On 01 Mar, 2020
Reviewer #2 agreed
On 01 Mar, 2020
Editor assigned
On 21 Jan, 2020
Submission checks complete
On 16 Jan, 2020
First submitted
On 27 Dec, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Trials.
Background: Critically ill infants with congenital heart disease (CHD) are often prescribed stress ulcer prophylaxis (SUP) to prevent upper gastrointestinal bleeding, despite the low incidence of stress ulcers and limited data on the safety and efficacy of SUP in infants. Recently, SUP has been associated with an increased incidence of hospital-acquired infections, community-acquired pneumonia and necrotizing enterocolitis. The objective of this pilot study is to investigate the feasibility of performing a randomized controlled trial to assess the safety and efficacy of withholding SUP in infants with congenital heart disease admitted to the cardiac intensive care unit.
Methods: A single center, prospective, double-blinded, randomized placebo-controlled pilot feasibility trial will be performed in infants with CHD admitted to the cardiac intensive care unit and anticipated to require respiratory support for > 24 hours. Patients will be randomized to receive a histamine-2 receptor antagonist (H2RA) or placebo until they are discontinued from respiratory support. Randomization will be performed within 2 strata defined by admission type (medical or surgical) and age (neonate, age <30 days, or infant, 1 month to 1 year). Allocation will be a 1:1 ratio using permuted blocks to ensure balanced allocations across the two treatment groups within each stratum. The primary outcomes include feasibility of screening, consent, timely allocation of study drug, and protocol adherence. The primary safety outcome is the rate of clinically significant upper gastrointestinal bleeding. The secondary outcomes are the difference in the relative and absolute abundance of the gut microbiota and functional microbial profiles between the two study groups. We plan to enroll 100 patients in this pilot study.
Discussion: Routine use of SUP to prevent upper gastrointestinal bleeding in infants is controversial due to a low incidence of bleeding events and concern for adverse effects. The role of SUP in infants with CHD has not been examined and there is equipoise on the risks and benefits of withholding this therapy. In addition, this therapy has been discontinued in other neonatal populations due to the concern for hospital-acquired infections and necrotizing enterocolitis. Furthermore, exploring changes to the microbiome after exposure to SUP may highlight the mechanisms by which SUP impacts potential microbial dysbiosis of the gut and its association with hospital-acquired infections. Assessment of the feasibility of a trial of witholding SUP in critically ill infants with CHD will facilitate planning of a larger multicenter trial of safety and efficacy of SUP in this vulnerable population.
Trial registration: Clinicaltrials.gov; NCT03667703; submitted September 12, 2018
Figure 1
This is a list of supplementary files associated with this preprint. Click to download.
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