Prematurity Related Ventilatory Control (PRE-VENT) - Specific Aim 2

• ClinicalTrials.gov Identifier: NCT03333161
• Recruitment Status: Completed
• First Posted: November 6, 2017
• Last Update Posted: September 21, 2021
• Sponsor: University of Alabama at Birmingham
• Collaborators: National Institutes of Health (NIH); National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Namasivayam Ambalavanan, University of Alabama at Birmingham

Study Description

Brief Summary:

To determine if late (at or beyond postnatal day 14) mild permissive hypercapnia is associated with reduction in apnea, bradycardia, and hypoxemic episodes and with improved stability of oxygenation.

Condition or disease	Intervention/treatment	Phase
Infant,Premature	Diagnostic Test: Cardiorespiratory monitoring	Not Applicable

Detailed Description:

Preterm infants who remain intubated or on nasal mechanical ventilation (IMV) at 14 days postnatal age, meet blood gas criteria, have transcutaneous carbondioxide (TcCO2) monitoring with TcCO2 values that trend and correlate appropriately with PaCO2, and are not judged too unstable by Attending neonatologist will qualify.

The investigators will use the data from the 96 hours of intensive multiparametric physiologic monitoring at 2 weeks postnatal age.

The first 24 hours of data collection will be the baseline data. Over the next 72 hours, the investigators will evaluate 3 interventions in a cross-over manner with the initial intervention randomly assigned: Intervention 1 (24-48h of data), Intervention 2 (48-72h of data) and Intervention 3 (72-96h of data).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: The investigators will use the data from the 96 hours of intensive multiparametric physiologic monitoring at 2 weeks postnatal age. The first 24 hours of the data collection will be the baseline data, followed by evaluation of 3 interventions in a cross-over manner, with the initial intervention randomly assigned (computer-generated): Intervention 1 (24-48h of data), Intervention 2 (48-72h), and Intervention 3 (72-96h). The interventions will be to adjust transcutaneous carbondioxide measurements (TcCO2) up or down by 5 mm Hg, while maintaining TcCO2 within usual safe thresholds.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prematurity-Related Ventilatory Control (PRE-VENT): Role in Respiratory Outcomes Clinical Research Centers (CRC)
• Actual Study Start Date: April 9, 2018
• Actual Primary Completion Date: March 30, 2021
• Actual Study Completion Date: March 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Higher TcCO2; The investigators will evaluate the effects of attempts to increase blood carbon dioxide levels within a narrow range of 5 mm Hg (well within the range of usual clinical practice) in a cross-over manner for 24 hours at a time, over a 4-day period, and use Cardiorespiratory Monitoring to evaluate control of breathing. The investigators will attempt to adjust PCO2 by 5 mm Hg higher from baseline (to max of 70 mm Hg), as long as pH is >7.2. The first 24 hours of the data collection will be the baseline data. Over the next 72 hours, the investigators will evaluate 3 interventions in a cross-over manner, with the initial intervention randomly assigned: Intervention 1 (24-48h of data; Increase TcCO2 by 5 mm Hg), Intervention 2 (48-72h; TcCO2 back to baseline), and Intervention 3 (72-96h; increase TcCO2 again by 5 mm Hg).	Diagnostic Test: Cardiorespiratory monitoring; We will use high resolution physiologic monitoring of Heart Rate, Respiratory Rate, Pulse oximetry, (and near-infrared monitoring as well as microcapnography in selected infants) to evaluate control of breathing (apnea, bradycardia, desaturations).
Active Comparator: Lower TcCO2; The investigators will evaluate the effects of attempts to decrease blood carbon dioxide levels within a narrow range of 5 mm Hg (well within the range of usual clinical practice) in a cross-over manner for 24 hours at a time, over a 4-day period, and use Cardiorespiratory Monitoring to evaluate control of breathing. The investigators will attempt to adjust PCO2 by 5 mm Hg lower than baseline (to minimum of 40 mm Hg), as long as pH is <7.45.	Diagnostic Test: Cardiorespiratory monitoring; We will use high resolution physiologic monitoring of Heart Rate, Respiratory Rate, Pulse oximetry, (and near-infrared monitoring as well as microcapnography in selected infants) to evaluate control of breathing (apnea, bradycardia, desaturations).

Outcome Measures

Primary Outcome Measures :

1. Hypoxemic episode [ Time Frame: During 24 hour time periods with targeted transcutaneous carbondioxide (TcCO2) ]
   Hypoxemic episode defined as as oxygen saturation by pulse oximetry (SpO2 )<85% for >10 seconds

Secondary Outcome Measures :

1. Bradycardic episode [ Time Frame: During 24 hour time periods with targeted TcCO2 ]
   Bradycardic episode defined as heart rate (HR) <100/min for >10 seconds
2. Apnea episodes [ Time Frame: During 24 hour time periods with targeted TcCO2 ]
   Apnea defined as Respiratory Rate (RR)=0 for >20 seconds, or RR=0 for >10 seconds + SpO2 <85% or HR <100/min
3. Hypoxemic time [ Time Frame: During 24 hour time periods with targeted TcCO2 ]
   Hypoxemic time defined as duration of time with SpO2 <85%
4. Bronchopulmonary dysplasia (BPD) [ Time Frame: 36 weeks PMA ]
   BPD defined using physiologic definition at 36w Post-Menstrual Age (PMA)

Eligibility Criteria

• Ages Eligible for Study: 1 Day to 15 Days (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Inborn infants weighing 401-1,000 grams on admission and/or 22w 0/7d to 28w 6/7d (<29 weeks) inclusive completed weeks of gestation
2. Infants eligible for full care and resuscitation as necessary, and surviving beyond 24 h of age
3. Enrollment in main study protocol (Aim 1 of PreVENT Apnea) at <1 week post-natal age
4. Informed consent from parent/guardian
5. This study will enroll the subset of infants from Aim 1 who are still intubated or on nasal IMV at 2 weeks postnatal age, meet blood gas criteria (arterial or capillary arterialized blood gas values done q12-24h, as most infants do not have an arterial line at 2 weeks: pH >7.25, PaCO2 >40 mm Hg), have TcCO2 monitoring with TcCO2 values that trend and correlate appropriately with PaCO2, and are not judged too unstable by the Attending neonatologist.

Exclusion Criteria:

1. Refusal or withdrawal of consent
2. Major congenital malformations (e.g., not including patent ductus arteriosus, small hernia)

Contacts and Locations

Locations

United States, Alabama

Regional Neonatal ICU and CCN, University of Alabama at Birmingham

Birmingham, Alabama, United States, 35233

Sponsors and Collaborators

University of Alabama at Birmingham

National Institutes of Health (NIH)

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Namasivayam Ambalavanan, MD; University of Alabama at Birmingham

  Study Documents (Full-Text)

Documents provided by Namasivayam Ambalavanan, University of Alabama at Birmingham:

Study Protocol and Statistical Analysis Plan  [PDF] October 26, 2017

More Information

• Responsible Party: Namasivayam Ambalavanan, Principal Investigator, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT03333161
• Other Study ID Numbers: UAB Neo 017; U01HL133536 ( U.S. NIH Grant/Contract )
• First Posted: November 6, 2017
• Last Update Posted: September 21, 2021
• Last Verified: September 2021

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 Namasivayam Ambalavanan, University of Alabama at Birmingham:

apnea of prematurity; bradycardia; hypoxemic episode; permissive hypercapnia

Additional relevant MeSH terms:

Premature Birth; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases