Comparison of Two Flow Rates of HHHFNC to Prevent Extubation Failure in Preterm Infants

Study Overview
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Brief Summary
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This is a randomized controlled trial (RCT) to evaluate the influence of two flow rates (6 liter/min versus 3 liter/min) of Heated-Humidified High-Flow-Nasal-Cannula (HHHFNC) on rates of extubation failure in mechanically ventilated preterm infants.

Detailed Description
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HHHFNC has been proposed as an alternative to nasal continuous positive airway pressure (nCPAP) in neonatal intensive care units (NICUs) for preventing extubation failure. In a recent international survey on periextubation practices in extremely preterm infants, nCPAP was the most common type of respiratory support used (84%) followed by nasal intermittent positive pressure ventilation (55%) and HHHFNC (33%). Moreover, HHHFNC appears to have efficacy and safety similar to those of nCPAP when applied immediately post-extubation to prevent extubation failure in preterm infants. and resulted in significantly less nasal trauma in the first 7 days post-extubation than nCPAP. However, the best flow rates of HHHFNC to prevent extubation failure remains to be known. This RCT aims to compare the efficacy and safety of postextubation respiratory support via HHHFNC at two different flow rates (6 L/min. versus 3 L/min) regarding successful extubation after a period of endotracheal positive pressure ventilation. We hypothesized that postextubation respiratory support via HHHFNC at a flow rate of 6 L/min. will result in a greater proportion of preterm infants being successfully extubated after a period of endotracheal positive pressure ventilation compared with HHHFNC at a flow rate of 3 L/min.

Official Title
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HHHFNC to Prevent Extubation Failure in Preterm Infants: A Randomized Controlled Trial

Conditions
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Prematurity, Mechanical Ventilation

Intervention / Treatment
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* Device: HHHFNC 6 liter minute
* Device: HHHFNC 3 liters/min


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants born at less than 37 weeks' gestation, required endotracheal intubation and positive pressure ventilation, and are considered ready for extubation by the clinical team. Infants will be enrolled after written informed parental consent is obtained. Exclusion Criteria: Suspected upper airway obstruction, congenital airway malformations, or major cardiopulmonary malformations

Ages Eligible for Study
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Minimum Age: 1 Hour
Maximum Age: 30 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 6 liter/min group<br>Infants will be extubated to a HHHFNC (Fisher and Paykel Healthcare , Auckland, New Zealand) at ﬂow rate of 6 L/min. Eligible infants will be enrolled while receiving mechanical ventilation. The timing of extubation will be determined by the clinical team and all infants will start caffeine prior to extubation. | Device: HHHFNC 6 liter minute<br>* Infants allocated to HHHFNC at 6 L/min. will be extubated to a HHHFNC flow of 6 L/min. Eligible infants will be enrolled while receiving mechanical ventilation. The timing of extubation will be determined by the clinical team and all infants will start caffeine prior to extubation.<br>|
| Active Comparator: 3 liter/min group<br>Infants will be extubated to HHHFNC (Fisher and Paykel Healthcare , Auckland, New Zealand) a ﬂow rate of 3 L/min. Eligible infants will be enrolled while receiving mechanical ventilation. The timing of extubation will be determined by the clinical team and all infants will start caffeine prior to extubation. | Device: HHHFNC 3 liters/min<br>* Infants allocated to HHHFNC at 3 L/min. will be extubated to a HHHFNC flow of 3 L/min. Eligible infants will be enrolled while receiving mechanical ventilation. The timing of extubation will be determined by the clinical team and all infants will start caffeine prior to extubation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extubation failure | Extubation failure criteria will be defined as follows: Apnea (respiratory pause >20 seconds), more than 6 episodes requiring physical stimulation in 6 hours or 1 requiring intermittent positive pressure ventilation. Respiratory acidosis with pH <7.25 and Peripheral arterial oxygen saturation (PaCO2) >65 mmHg. ( >15% sustained increase in FiO2 from extubation. 4. Cardiovascular collapse (heart rate <60 beats per minute or shock. 5. Persistent marked/severe retractions. Extubation failure will be deemed to occur if any single criterion was met in any one of the 7 days after extubation. The decision to reintubate an infant and mechanical ventilation variables and subsequent extubation attempts after reintubation will be managed at the discretion of the clinical team. | the 7 days after extubation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Death within the 96 hour post-extubation period or at any time after randomization. | within the 96 hour post-extubation period or at any time after with expected average of 5 weeks | 
| Total duration of mechanical ventilation | Total duration of mechanical ventilation during NICU admission | During NICU admission with expected average of 5 weeks | 
| Total duration of oxygen supplementation | Total duration of oxygen supplementation during NICU admission | During NICU admission with expected average of 5 weeks | 
| Bronchopulmonary dysplasia (BPD) | BPD defined by oxygen requirement at 36 weeks' post-menstrual age. | at 36 weeks' post-menstrual age. | 
| Severe BPD | Severe BPD defined as oxygen requirement with fraction of inspired oxygen (FiO2) >0.30 or need for positive pressure support at 36 weeks' post-menstrual age. | at 36 weeks' post-menstrual age. | 
| The combined outcome variables of death before 36 weeks PMA or BPD | The combined outcome variables of death before 36 weeks PMA or BPD will be used to adjust for occurrence of death after extubation but before the time of assessment of BPD. | at 36 weeks' post-menstrual age. | 
| The combined outcome variables of death before 36 weeks PMA or severe BPD | The combined outcome variables of death before 36 weeks' post-menstrual age (PMA) or severe BPD will be used to adjust for occurrence of death after extubation but before the time of assessment of BPD. | at 36 weeks' post-menstrual age | 
| Other neonatal morbidities (intracranial hemorrhage, pneumothorax, patent ductus arteriosus, necrotizing enterocolitis, and retinopathy of prematurity) | The occurrence of neonatal morbidities occurring before, during the 96 hours post-extubation, and at any time thereafter will be documented (intracranial hemorrhage, pneumothorax, patent ductus arteriosus, necrotizing enterocolitis, and retinopathy of prematurity). | baseline, during the 96 hours post-extubation, and at any time thereafter during NICU stay with an expected average of 5 weeks |