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

• ClinicalTrials.gov Identifier: NCT03670732
• Recruitment Status: Recruiting
• First Posted: September 14, 2018
• Last Update Posted: May 28, 2020
• Sponsor: Women and Infants Hospital of Rhode Island
• Information provided by (Responsible Party): Martin Keszler, Women and Infants Hospital of Rhode Island

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Prematurity; Respiratory Distress Syndrome; Apnea of Prematurity	Other: continuous positive airway pressure; Other: nasal intermittent positive pressure ventilation	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Crossover non-inferiority trial
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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.
• Actual Study Start Date: September 30, 2017
• Estimated Primary Completion Date: June 30, 2022
• Estimated Study Completion Date: June 30, 2022

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: NIPPV

Outcome Measures

Primary Outcome Measures :

1. Number of Apnea/bradycardia events [ Time Frame: Duration of intervention (12 hours) ]
   Number of episodes of apnea and/or bradycardia that trigger alarm on the bedside monitor

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: up to 6 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Martin Keszler, MD; 401 274 1122 ext 47490; mkeszler@wihri.org

Contact: Lisa Grady, MD; 401 274 1122; LGrady@wihri.org

Locations

United States, Rhode Island

Women and Infants Hospital of Rhode Island; Recruiting

Providence, Rhode Island, United States, 02905

Contact: Martin Keszler, MD 401-274-1122 ext 47490 mkeszler@wihri.org

Contact: Ashish Gupta, MD 401 274 1122 ext 47466 AKGupta@wihri.org

Sponsors and Collaborators

Women and Infants Hospital of Rhode Island

Investigators

• Study Director: Sunil Shaw, PhD; Brown University

More Information

• Responsible Party: Martin Keszler, Professor of Pediatrics, Associate Director of NICU, Director of Respiratory Care, Women and Infants Hospital of Rhode Island
• ClinicalTrials.gov Identifier: NCT03670732
• Other Study ID Numbers: 1010049; WIH 17-0037 ( Other Identifier: Women and Infants Hospital of Rhode Island )
• First Posted: September 14, 2018
• Last Update Posted: May 28, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Martin Keszler, Women and Infants Hospital of Rhode Island:

Continuous positive airway pressure; Nasal intermittent positive pressure ventilation; Mean airway pressure; Apnea; Bradycardia; Prematurity

Additional relevant MeSH terms:

Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Premature Birth; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications