Close Loop Smart Weaning for INO With PPHN

May 12, 2026 updated by: Children's Hospital of Fudan University

Close Loop Smart Weaning Protocol for Inhaled Nitric Oxide Therapy With PPHN

In contemporary clinical practice concerning the administration of inhaled nitric oxide (iNO) within neonatal intensive care units (NICUs), a stepwise reduction approach is frequently employed in accordance with established neonatal guidelines. Nonetheless, the comparative advantages of a linear reduction strategy-characterized by a gradual decrease in inhalation concentration-over the traditional stepwise method in terms of efficacy and safety have yet to be conclusively established. Furthermore, existing iNO delivery devices necessitate that healthcare professionals manually adjust parameters at intervals dictated by the patient's condition. This reliance on subjective clinical judgment often results in variability and a lack of standardization in the duration of the weaning process. Additionally, the protracted and intricate nature of the weaning procedure considerably heightens the workload for healthcare staff. Importantly, the development of a scientifically grounded, standardized, and real-time feedback mechanism for weaning may enhance clinical outcomes for patients and mitigate the risks associated with inappropriate weaning practices or inconsistent manual interventions. Consequently, this study seeks to leverage the newly introduced "intelligent closed-loop weaning" feature of the latest generation of iNO devices to facilitate automated linear concentration reduction during the weaning process. This innovation aims to alleviate the burden on healthcare personnel while establishing a more standardized and scientifically robust weaning protocol. However, it is noteworthy that there is currently a lack of clinical evidence, both domestically and internationally, regarding the safety and efficacy of this device's weaning protocol, underscoring the urgent need to validate its safety and effectiveness in real-world clinical settings.

Study Overview

Status

Status

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

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

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

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.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
      • Shanghai, China
        • Recruiting
        • Children's Hospital of Fudan University
        • Contact:

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. The administration of inhaled nitric oxide (iNO) has commenced or is anticipated to commence for a duration of 24 hours or more, based on a clinical diagnosis of persistent pulmonary hypertension of the newborn (PPHN);
  2. There is a demonstrable positive response to iNO treatment;
  3. The iNO delivery system employed is appropriate and meets the conditional requirements, featuring an intelligent closed-loop offline functionality;
  4. The guardian or legal representative possesses a comprehensive understanding of the potential benefits and risks associated with participation in this study and has expressed a willingness to consent by signing the informed consent document.

Exclusion Criteria:

  1. There are established contraindications associated with the use of nitric oxide, which include the following conditions:

    1. Severe hypoplasia of the left heart or duct-dependent congenital heart disease;
    2. Life-threatening congenital anomalies and congestive heart failure;
    3. Congenital methemoglobinemia;
    4. Significant hemorrhagic events, such as intracranial hemorrhage, intraventricular hemorrhage, and pulmonary hemorrhage.
  2. Patients with chronic pulmonary conditions and other refractory diseases are not permitted to initiate withdrawal from the inhaled nitric oxide (iNO) treatment within a seven-day period following its administration.
  3. In cases where there is no observable response to iNO or if the duration of use is less than 30 minutes, a strict tapering protocol for withdrawal is not required.
  4. If the concentration of iNO treatment exceeds 20 parts per million (ppm) during the initiation phase or if the starting concentration for withdrawal is below 20 ppm, specific considerations must be taken into account.
  5. Participation in concurrent clinical trials involving other pharmacological agents or medical devices is prohibited.
  6. The investigator may determine that participation in this study is not appropriate for certain individuals.

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: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

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: Inhaled Nitric Oxide (iNO), the initial concentration of NO withdrawal is 20ppm.

In the initial phase of the study, a total of 10 participants are enrolled in a non-controlled single-group pre-trial.

The subsequent phase is organized into two distinct groups, each comprising 10 participants, resulting in a total of 20 subjects. The groups are categorized as follows:

① The experimental group, which utilizes an intelligent closed-loop offline system operating in a linear decline mode;

② The control group, which employs an intelligent closed-loop offline system functioning in a step decline mode.
Device: Nitric Oxide Generation and Delivery System

The Nitric Oxide Generation and Delivery System is used to deliver nitric oxide for inhalation therapy into the inspiratory limb of the patient breathing circuit in a way that provides a constant concentration of nitric oxide (NO), as set by the user, to the patient throughout the inspired breath.

iNO devices with intelligent closed-loop offline function are required to meet the import and discharge standards. The initial concentration of NO withdrawal is 20ppm. In accordance with the withdrawal criteria outlined in the Chinese Guidelines, it is essential to conduct a comprehensive efficacy evaluation prior to initiating withdrawal. Furthermore, the process of inhaled nitric oxide (iNO) evacuation should commence only if specific conditions are satisfied.

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
The occurrence of nitric oxide (NO) rebound hypoxia during the evacuation process
Time Frame: Completion of evacuation (expected day 2 of evacuation)
The occurrence of nitric oxide (NO) rebound hypoxia during the evacuation process, operationally defined as the frequency of instances in which peripheral capillary oxygen saturation (SpO2) decreased by more than 5% and the fraction of inspired oxygen (FiO2) increased by 15% in order to maintain partial pressure of arterial oxygen (PaO2) above 60 mmHg (with SpO2 ≥ 90%) during the evacuation of NO
Completion of evacuation (expected day 2 of evacuation)
The total duration of inhaled nitric oxide (iNO) evacuation
Time Frame: Completion of evacuation (expected day 2 of evacuation)
The entire length of time required to remove or discontinue the use of iNO.
Completion of evacuation (expected day 2 of evacuation)

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
Device Alarm Frequency
Time Frame: Completion of evacuation (expected day 2 of evacuation)
The frequency of device alarms recorded during the evacuation process.
Completion of evacuation (expected day 2 of evacuation)
NO Concentration Adjustments
Time Frame: Completion of evacuation (expected day 2 of evacuation)
The total number of adjustments made to knobs and settings for nitric oxide concentration during evacuation.
Completion of evacuation (expected day 2 of evacuation)
Mechanical Ventilation Duration
Time Frame: Completion of evacuation (expected day 2 of evacuation)
The duration of mechanical ventilation.
Completion of evacuation (expected day 2 of evacuation)
Adverse Events Incidence
Time Frame: Completion of evacuation (expected day 2 of evacuation)
The incidence of adverse events associated with nitric oxide treatment.
Completion of evacuation (expected day 2 of evacuation)
Complication Rate
Time Frame: Completion of evacuation (expected day 2 of evacuation)
The complication rate, specifically focusing on Grade 3-4 intraventricular hemorrhage, intraventricular plasmalacia, moderate to severe bronchopulmonary dysplasia, retinopathy of prematurity necessitating intervention, patent ductus arteriosus requiring either medical or surgical management, pulmonary hemorrhage, and air leak syndrome.
Completion of evacuation (expected day 2 of evacuation)
ECMO Utilization Rate
Time Frame: Completion of evacuation (expected day 2 of evacuation)
The proportion of cases that required extracorporeal membrane oxygenation (ECMO).
Completion of evacuation (expected day 2 of evacuation)
Mortality Rate Before Discharge
Time Frame: Completion of evacuation (expected day 2 of evacuation)
The mortality rate prior to discharge.
Completion of evacuation (expected day 2 of evacuation)
Healthcare Utilization Preferences
Time Frame: Completion of evacuation (expected day 2 of evacuation)
Scores obtained from questionnaires assessing preferences for healthcare utilization.The Likert Scale is used in the questionnaires to measure respondents' attitudes, preferences, or perceptions. It typically ranges from 1 to 5 points, where 1 represents "Strongly Disagree" and 5 represents "Strongly Agree". Respondents select the level that best reflects their opinion, allowing researchers to quantify subjective data and analyze trends effectively.
Completion of evacuation (expected day 2 of evacuation)

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 of Fudan University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Lin Yuan, Children's Hospital of Fudan University

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 1, 2025

Primary Completion (Estimated)

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.
December 31, 2026

Study Completion (Estimated)

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.
December 31, 2026

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).
February 12, 2025

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 12, 2025

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 18, 2025

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.
May 13, 2026

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.
May 12, 2026

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.
May 1, 2026

More Information

Terms related to this study

Keywords

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.
  • Close-iNO Study

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

No

Studies a U.S. FDA-regulated device product

No

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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