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

Tracking Information

• First Submitted Date: November 2, 2017
• First Posted Date: November 6, 2017
• Last Update Posted Date: September 21, 2021
• Actual Study Start Date: April 9, 2018
• Actual Primary Completion Date: March 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 4, 2017)

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

Original Primary Outcome Measures (submitted: November 2, 2017)

Hypoxemic episode [ Time Frame: During 24h time periods with targeted TcCO2 ]

Hypoxemic episode defined as as SpO2 <85% for >10s

Current Secondary Outcome Measures (submitted: November 4, 2017)

• Bradycardic episode [ Time Frame: During 24 hour time periods with targeted TcCO2 ]
  Bradycardic episode defined as heart rate (HR) <100/min for >10 seconds
• 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
• Hypoxemic time [ Time Frame: During 24 hour time periods with targeted TcCO2 ]
  Hypoxemic time defined as duration of time with SpO2 <85%
• Bronchopulmonary dysplasia (BPD) [ Time Frame: 36 weeks PMA ]
  BPD defined using physiologic definition at 36w Post-Menstrual Age (PMA)

Original Secondary Outcome Measures (submitted: November 2, 2017)

• Bradycardic episode [ Time Frame: During 24h time periods with targeted TcCO2 ]
  Bradycardic episode defined as HR <100/min for >10s
• Apnea episodes [ Time Frame: During 24h time periods with targeted TcCO2 ]
  Apnea defined as RR=0 for >20s, or RR=0 for >10s + SpO2 <85% or HR <100/min
• Hypoxemic time [ Time Frame: During 24h time periods with targeted TcCO2 ]
  Hypoxemic time defined as duration of time with SpO2 <85%
• Bronchopulmonary dysplasia (BPD) [ Time Frame: 36w PMA ]
  BPD defined using physiologic definition at 36w Post-Menstrual Age

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Prematurity Related Ventilatory Control (PRE-VENT) - Specific Aim 2
• Official Title: Prematurity-Related Ventilatory Control (PRE-VENT): Role in Respiratory Outcomes Clinical Research Centers (CRC)
• 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.

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 Type: Interventional
• Study Phase: Not Applicable

Study Design

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

• Condition: Infant,Premature

Intervention

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).

Study Arms

• 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).

  Intervention: Diagnostic Test: Cardiorespiratory monitoring
• 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.

  Intervention: Diagnostic Test: Cardiorespiratory monitoring

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 2, 2017): 25
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: March 30, 2021
• Actual Primary Completion Date: March 30, 2021 (Final data collection date for primary outcome measure)

Eligibility 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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Day to 15 Days (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03333161
• Other Study ID Numbers: UAB Neo 017; U01HL133536 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Namasivayam Ambalavanan, University of Alabama at Birmingham
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Alabama at Birmingham
• Original Study Sponsor: Same as current

Collaborators

• National Institutes of Health (NIH)
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

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

• PRS Account: University of Alabama at Birmingham
• Verification Date: September 2021