CPAP vs.Unsynchronized NIPPV at Equal Mean Airway Pressure (NICA)

Nasal Intermittent Positive Pressure Ventilation vs. Nasal Continuous Positive Airway Pressure at Equivalent Mean Airway Pressure in Preterm Infants: Effect on Oxygenation, CO2 Elimination, Work of Breathing and Frequency of Cardio-respiratory Events.

This study seeks to determine if standard continuous positive airway pressure, known as CPAP is as effective as a more complicated approach that generates intermittent increases in airway pressure applied to the nostrils via a breathing machine. The latter is known as NIPPV and requires costly equipment to operate. Previous studies did not ensure that the average pressure applied to the lungs was equal and thus did not make for a fair comparison. The investigators believe that when the same average pressure is applied with the two techniques, CPAP is just as effective as NIPPV and may have fewer side effects, such as blowing air into the stomach. Each baby will receive CPAP or NIPPV in a random sequence for a period of 12 hours, followed by 12 hours on the alternate technique.

Study Overview

• Status: Unknown
• Conditions: Respiratory Distress Syndrome; Apnea of Prematurity; Prematurity
• Intervention / Treatment: Other: continuous positive airway pressure; Other: nasal intermittent positive pressure ventilation

Detailed Description

This is a pilot clinical trial to evaluate the comparative effectiveness of two commonly used types of non-invasive respiratory support. Preterm infants < 34 weeks gestational age, who are stable on either of the two modalities of support will be studied in a cross-over study design, such that each subject acts as his/her own control. The study will assess the relative efficacy of these modalities when used with equal mean airway pressure comparing measures of oxygenation, CO2 removal, apnea/bradycardia/desaturation events and work of breathing. The initial phase of the study is complete and preliminary analysis supports the hypothesis that there is no difference between the modalities when the mean airway pressure is equal. However we recognized that use of the RAM cannula, which does not transmit pressure effectively is an important study limitation. The findings are valid, but may only be applicable to this interface, which is widely used, but increasingly recognized as flawed. We are now extending the study to determine if the findings will be the same when short bi-nasal prongs are used.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Martin Keszler, MD; Phone Number: 47490 401 274 1122; Email: mkeszler@wihri.org
• Study Contact Backup: Name: Lisa Grady, MD; Phone Number: 401 274 1122; Email: LGrady@wihri.org

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Recruiting
      • Women and Infants Hospital of Rhode Island
      • Contact: Martin Keszler, MD; Phone Number: 47490 401-274-1122; Email: mkeszler@wihri.org
      • Contact: Ashish Gupta, MD; Phone Number: 47466 401 274 1122; Email: AKGupta@wihri.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 months (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Gestational Age 23-34 completed weeks
• Stable on non- invasive respiratory support for at least 24h
• CPAP level of 7-12 cmH2O or NIPPV with MAP 7-12 cmH2O
• FiO2 requirement of <0.40

Exclusion Criteria:

• Clinical instability as judged by the clinical team
• FiO2 requirement of > 0.40 for more than 60 min.
• >10 apnea/bradycardia/desaturation events in past 24 h requiring moderate or vigorous stimulation.
• Anticipated intubation within next 24 h.
• Active abdominal pathology (Spontaneous Intestinal Perforation, confirmed or suspected Necrotizing Enterocolitis, bowel obstruction).
• Hemodynamically significant patent ductus arteriosus (PDA)
• Anticipated weaning off non-invasive support in the next 24 h.
• Any major congenital anomalies, congenital heart disease (other than PDA, atrial septal defect or ventricular septal defect) and cardiac arrhythmias
• Lack of study equipment or personnel
• Lack of parental consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: CPAP first; The intervention is application of continuous positive airway pressure (CPAP). The order of the two interventions of this crossover study is randomized but each subject will be exposed to both interventions. The period of CPAP will be compared to the period of NIPPV.	Other: continuous positive airway pressure; Continuous positive airway pressure is applied for 12 hours at a mean airway pressure that is the same as the subject was receiving prior to entry into the study; Other Names: CPAP; Other: nasal intermittent positive pressure ventilation; NIPPV is applied for 12 hours at a mean airway pressure that is the same as the subject was receiving prior to entry into the study; Other Names: NIPPV
ACTIVE_COMPARATOR: NIPPV first; The intervention is application of nasal intermittent positive pressure ventilation (NIPPV). The order of the two interventions of this crossover study is randomized but each subject will be exposed to both interventions. The period of CPAP will be compared to the period of NIPPV.	Other: continuous positive airway pressure; Continuous positive airway pressure is applied for 12 hours at a mean airway pressure that is the same as the subject was receiving prior to entry into the study; Other Names: CPAP; Other: nasal intermittent positive pressure ventilation; NIPPV is applied for 12 hours at a mean airway pressure that is the same as the subject was receiving prior to entry into the study; Other Names: NIPPV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Apnea/bradycardia events	Number of episodes of apnea and/or bradycardia that trigger alarm on the bedside monitor	Duration of intervention (12 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of of desaturation events	Number of episodes of pulse oximetry readings that trigger alarm on the bedside monitor	Duration of intervention (12 hours)
Mean oxygen saturation by pulse oximetry and proportion of time below 88%	Mean oxygen saturation by pulse oximetry and proportion of time at saturation <88%	Duration of intervention (12 hours)
Mean transcutaneous PCO2 and proportion of time >55 torr	Mean transcutaneous PCO2 and proportion of time at PCO2 > 55 torr	Duration of intervention (12 hours)
Mean fraction of inspired oxygen	Mean fraction of inspired oxygen (FIO2)	Duration of intervention (12 hours)
Mean respiratory rate	Mean respiratory rate	Duration of intervention (12 hours)
Mean degrees of phase lag by RIP	Estimate of work of breathing based on phase angle as determined by respiratory inductive plethysmography	Duration of intervention (12 hours)
Number of episodes of feeding intolerance	number of instances of interruption of feeding, abdominal radiographs	Duration of intervention (12 hours)
Instances of treatment failure	Inability to tolerate assigned treatment by pre-defined criteria	Duration of intervention (12 hours)

Collaborators and Investigators

• Sponsor: Women and Infants Hospital of Rhode Island
• Investigators: Study Director: Sunil Shaw, PhD, Brown University

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 30, 2017
• Primary Completion (ANTICIPATED): June 30, 2022
• Study Completion (ANTICIPATED): June 30, 2022

Study Registration Dates

• First Submitted: September 12, 2018
• First Submitted That Met QC Criteria: September 12, 2018
• First Posted (ACTUAL): September 14, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 28, 2020
• Last Update Submitted That Met QC Criteria: May 26, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Prematurity; Continuous positive airway pressure; Apnea; Bradycardia; Nasal intermittent positive pressure ventilation; Mean airway pressure
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Infant, Premature, Diseases; Premature Birth; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn
• Other Study ID Numbers: 1010049; WIH 17-0037 (OTHER: Women and Infants Hospital of Rhode Island)

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