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

Study Overview
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Brief Summary
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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
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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).

Official Title
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Prematurity-Related Ventilatory Control (PRE-VENT): Role in Respiratory Outcomes Clinical Research Centers (CRC)

Conditions
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Infant,Premature

Intervention / Treatment
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* Diagnostic Test: Cardiorespiratory monitoring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Infants eligible for full care and resuscitation as necessary, and surviving beyond 24 h of age Enrollment in main study protocol (Aim 1 of PreVENT Apnea) at <1 week post-natal age Informed consent from parent/guardian 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: Refusal or withdrawal of consent Major congenital malformations (e.g., not including patent ductus arteriosus, small hernia)

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 15 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Higher TcCO2<br>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<br>* 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).<br>|
| Active Comparator: Lower TcCO2<br>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<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypoxemic episode | Hypoxemic episode defined as as oxygen saturation by pulse oximetry (SpO2 )<85% for >10 seconds | During 24 hour time periods with targeted transcutaneous carbondioxide (TcCO2) | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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apnea of prematurity, bradycardia, hypoxemic episode, permissive hypercapnia