Nitric Oxide During Cardiopulmonary Bypass in Neonates to Reduce Risk of Acute Kidney Injury

February 5, 2020 updated by: Children's Hospital Medical Center, Cincinnati

Efficacy of Nitric Oxide Administration During Cardiopulmonary Bypass in Neonates at Reducing the Risk of Acute Kidney Injury: a Preliminary Double-blind Randomized Controlled Trial

Acute kidney injury following cardiac surgery for congenital heart defects in children is a major cause of both short- and long-term morbidity and mortality, affecting up to 60% of high risk patients. Despite effort, to date, no successful therapeutic agent has gained widespread success in preventing this postoperative decline in renal function. Based on preliminary data available in the literature, we hypothesize that nitric oxide (gNO), administered during cardiopulmonary bypass (CPB), may reduce the risk of acute kidney injury (AKI) via mechanisms of reduced inflammation and vasodilation. In this pilot study, 40 neonates undergoing cardiac surgery will be randomized to receive intraoperative administration of 20 ppm of nitric oxide to the oxygenator of the cardiopulmonary bypass circuit or standard CPB with no additional gas.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 1 month (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Neonates (≤31 days) undergoing cardiac surgery with cardiopulmonary bypass for congenital heart disease

Exclusion Criteria:

  • 1. Failure to obtain informed consent from parent/guardian,
  • Clinical signs of preoperative persistent elevated pulmonary vascular resistance,
  • Emergency surgery,
  • Episode of cardiac arrest within 1 week before surgery,
  • Recent treatment with steroids and/or a condition that may require treatment with steroids (excluding steroid administration specifically for CPB),
  • Use of inhaled NO (iNO) immediately prior to surgery,
  • Structural renal abnormalities by ultrasound,
  • Preoperative AKI,
  • Use of other investigational drugs,
  • Weight less than <2.2 kg,
  • Gestational age <36 weeks,
  • Major extracardiac congenital anomalies.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: gNO Group
Participants in the treatment group will receive gNO added to the oxygenator gas flow at 20 ppm throughout the duration of cardiopulmonary bypass.
Drug: gases Nitric Oxide (gNO)
Participants in the intervention group will receive gNO blended into the fresh gas flow of the cardiopulmonary bypass (CPB) oxygenator and maintained at 20 ppm via an Ikaria INO Max DSIR (Mallinckrodt Pharmaceuticals, St. Louis, Missouri, USA), with continuous sampling of NO and NO2 concentration from a port adjacent to the oxygenator. The gNO delivery will be initiated when the patient is on CPB and stopped once the patient comes off CPB.
No Intervention: Control Group
Participants in the control group will receive standard conduction of cardiopulmonary bypass.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Acute Kidney Injury
Time Frame: up to 72 hours postoperative
Occurrence of acute kidney defined by the Kidney Disease Improving Global Outcomes (KDIGO) diagnostic classification (employing both serum creatinine and urine output criteria).
up to 72 hours postoperative
Glomerular Filtration Rate
Time Frame: up to 72 hours postoperative
Postoperative glomerular filtration rate (GFR) measured using serum cystatin C.
up to 72 hours postoperative

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Structural Kidney Injury
Time Frame: up to 72 hours postoperative
Assessed by measurement of urine biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18) liver-type fatty acid-binding protein (L-FABP), and urinary nitrate.
up to 72 hours postoperative
Low cardiac output syndrome (LCOS)
Time Frame: up to 48 hours postoperative

Occurence of low cardiac output syndrome (LCOS) defined as any of the following at any time during the first 48 hours postoperative:

  1. Lactate >6mmol/l and central venous saturation (ScvO2) <60% (or SaO2-ScvO2 difference greater than 35% in a single ventricle),
  2. Vasoactive inotropic score (VIS)24 ≥ 10,
  3. Extracorporeal Membrane Oxygenation (ECMO).
up to 48 hours postoperative
Duration of mechanical ventilation
Time Frame: up to 2 weeks from admission to CICU to extubation
hours/days
up to 2 weeks from admission to CICU to extubation
Length of cardiac intensive care unit (CICU) stay
Time Frame: up to 2 weeksfrom admission to CICU to discharge from CICU
days
up to 2 weeksfrom admission to CICU to discharge from CICU
Length of hospital stay
Time Frame: up to 30 days from hospital admission to discharge
days
up to 30 days from hospital admission to discharge
Inotrope free days
Time Frame: up to 30 days after surgery to CICU discharge
days
up to 30 days after surgery to CICU discharge
ECMO free days
Time Frame: up to 2 weeks after surgery to CICU discharge
Extracorporeal Membrane Oxygenation free days
up to 2 weeks after surgery to CICU discharge
Closed sternum days
Time Frame: up to 2 weeks from postoperative CICU admission to discharge
days
up to 2 weeks from postoperative CICU admission to discharge
Time to negative fluid balance
Time Frame: up to 2 weeks from CICU admission to outcome reached
hours/days
up to 2 weeks from CICU admission to outcome reached
Urine Output
Time Frame: up to two weeks from CICU admission to discharge
ml
up to two weeks from CICU admission to discharge
Use of peritoneal dialysis
Time Frame: up to two weeks from CICU admission to discharge
yes/no
up to two weeks from CICU admission to discharge
Cardiac arrest
Time Frame: up to two weeks from CICU admission to discharge
yes/no
up to two weeks from CICU admission to discharge
Use of postoperative inhaled Nitric Oxide (iNO)
Time Frame: up to two weeks from CICU admission to discharge
yes/no, indication, dose
up to two weeks from CICU admission to discharge

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Children's Hospital Medical Center, Cincinnati

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 20, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 20, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 20, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 19, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 5, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 6, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 6, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 5, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CIN001-gNO to prevent AKI

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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