Comparison of CPAP Machines With Reusable vs Disposable Circuits

Study Overview
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Brief Summary
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The study aims to assess the basic functionality of a newly designed CPAP machine with reusable circuits to existing machines with disposable circuits, for treatment of newborn infants diagnosed with respiratory distress syndrome. The assessment will compare a comprehensive list of physiological parameters over the first 72 hours of treatment, and will also monitor rates of side effects and adverse events. The null hypothesis is that infants treated on the two categories of machine (reusable vs disposable) will not differ in relation to key physiological parameters by more than 0.63 standard deviations.

Detailed Description
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One of the commonest sources of serious newborn morbidity and mortality is difficulty with breathing. When this occurs, three main types of supportive therapy are available to increase the provision of oxygen to cells: a) passive provision of oxygen-enriched gases (i.e., higher than the 21% O2 found in the earth's atmosphere) through tubes in the nostrils, or by putting a hood over the baby's head and enriching the gases under that hood; b) provision of room air or oxygen-enriched gasses under pressure, frequently performed using a method called continuous positive airway pressure [CPAP] therapy; and/or c) by using a machine that is able to breath on behalf of the baby, most commonly referred to as mechanical ventilation [MV]. Passive therapy is the least invasive method but is also of limited benefit, particularly for infants born preterm. CPAP is more effective than passive methods because continuous distending pressure to the lungs allows better oxygen exchange; however, the distending pressure increases the risk of damage to the lung. MV is the only method that can be used on babies without a neurological impulse to breath, but the mechanical breathing action can damage the lungs, and MV is usually provided through a tube inserted into the lungs which increases the risk of lung infection; MV machines are also significantly more expensive than CPAP machines. In high resource settings, CPAP is now the preferred method of providing oxygen for infants where passive therapy is insufficient, because of the lower infection risk, lower risk of lung damage, and relative ease of clinical care. CPAP is increasingly recommended for low resource settings, but the CPAP machines used in high resource settings are too expensive for low resource settings due to high-priced consumables ($US50-200/baby), and are usually unusable in low resource settings because they require 'medical air' (clean air in a cylinder, or through a piped wall system) with which to blend 100% oxygen. Low cost 'indigenous' machines ('jury-rigged' by hospital staff) have also been developed, but these do not provide the heated, humidified and blended gasses, that are recommended for CPAP. This study seeks to evaluate a novel CPAP machine that provides heated, humidified, blended gasses, in line with recommendations for high-resource settings, while massively reducing costs by including re-usable tube sets and humidifiers that can be autoclaved, and with an on-board air-compressor to allow use in a broader range of clinical settings. By reducing the cost per CPAP treatment, such a machine can dramatically increase the number of hospitals in low resource settings that can provide high quality CPAP treatment.

Official Title
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Randomised Trial Comparing CPAP Machines With Reusable vs Disposable Circuits

Conditions
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Respiratory Distress Syndrome, Newborn

Intervention / Treatment
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* Device: CPAP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants born at Ramaiah Medical College hospital ('inborn infants'); Infants born elsewhere, and admitted to Ramaiah Medical College hospital under 6 hours of age (outborn infants); Infants with a gestational age at birth (weeks +days) in the range ≥ 28+0 to ≤ 36+6; Infants thought to have RDS (clinically diagnosed after onset of respiratory distress <6 hours of age, sometimes confirmed by X-ray showing homogenous bilateral opacity) who would routinely be provided CPAP therapy; and Infants <24 hours old at the time of fulfilling other inclusion criteria. Exclusion Criteria: Infants with a 1-minute Apgar score <3 (as a marker of severe birth asphyxia); Infants who received MV prior to randomisation; Infants with suspected meconium aspiration syndrome will be excluded to avoid any imbalance in this condition across groups; Infants clinically suspected to have another specified serious condition as their main disease process, diagnosed prior to randomisation, specifically: cardiac anomaly, other congenital malformation with respiratory sequelae, septicaemia, pulmonary haemorrhage, pneumothorax, meningitis, poor respiratory effort or recurrent apnoea, or brain haemorrhage (IVH Grades III or IV); Infants who have an airway abnormality precluding the use of the standard CPAP interface proposed for this study (e.g., Pierre-Robin sequence, cleft lip or cleft palate) or who have a neuromuscular condition that interferes with respiration; Any infant whose treating clinician believes should not be randomised due to some other condition, or for any other reason (reason to be documented).

Ages Eligible for Study
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Minimum Age: 1 Minute
Maximum Age: 24 Hours

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dolphin CPAP<br>CPAP machine with oxygen intake and an on-board air compressor, and integrated blender and humidifier, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. [Also includes built-in Massimo pulse oximeter, though this is not used for this study, to prevent differential measurement error in SpO2 measurement] | Device: CPAP<br>* CPAP therapy<br>|
| Active Comparator: Fisher-Paykel CPAP<br>Fisher-Paykel (F&P) CPAP machine with separate oxygen and medical air intakes, with third-party FP-compliant blender, and F&P blender, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. | Device: CPAP<br>* CPAP therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FiO2 | Fraction of inspired oxygen (FiO2), measured as a change from baseline as shown on the two machines. Note. Outcome contaminated. An SpO2 target of 90-95% reflects currently recommended practice for neonates; when SpO2 exceeds the target, FiO2 should be reduced. The majority of readings were at SpO2 > 95%, so FiO2 for these SpO2 readings reflects oxygen provided, not oxygen required to achieve the recommended SpO2 target range (i.e., the FiO2 provided was excessive, by an unknown amount). | 6, 12, 24, 48 and 72 hours after treatment commencement | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SpO2 | Oxygen saturation by pulse oximetry (SpO2), measured as a change from baseline Note. Outcome contaminated. An SpO2 target of 90-95% reflects currently recommended practice for neonates. The majority of readings were at SpO2 > 95%, above SpO2 target (90-95%). | 6, 12, 24, 48 and 72 hours after treatment commencement | 
| Respiratory Rate | Respiratory rate (breaths/minute), measured as a change from baseline | 6, 12, 24, 48 and 72 hours after treatment commencement | 
| Arterial pH | pH measured as a change from baseline (where measured) | 6, 12, 24, 48 and 72 hours after treatment commencement (where available) | 
| Partial Pressure of Arterial Oxygen (PaO2) | PaO2 measured as a change from baseline (where measured) | 6, 12, 24, 48 and 72 hours after treatment commencement (where available) | 
| Partial Pressure of Arterial Carbon Dioxide (PaCO2) | PaCO2 measured as a change from baseline (where measured) | 6, 12, 24, 48 and 72 hours after treatment commencement (where available) | 
| Number of Participants Who Died or Needed Intubation and/or Mechanical Ventilation, as a Measure of CPAP Failure, Measured to Date and Time of Cessation of CPAP Treatment | Death or need for intubation and mechanical ventilation as demonstrated by an FiO2 requirement ≥ 60% for ≥ 1 hour to maintain SpO2 at 90-95% Note. An SpO2 target of 90-95% reflects currently recommended practice for neonates. FiO2 and SpO2 at time of intubation and ventilation not separately recorded, so we report this endpoint as recorded by clinicians, assuming that they have verified FiO2 [≥ 60% for ≥ 1 hour] and SpO2 [targeting 90-95%] requirements at the time of intubation and ventilation. If SpO2 was actually >95% (not 90-95%) at the time of intubation and ventilation, then FiO2 would be higher than required to meet the target range, by an unknown amount (possibly not meeting the FiO2 threshold of ≥ 60% for ≥ 1 hour, required to justify intubation and ventilation). We note this potential source of contamination because the results of Outcome #2 show that the majority of SpO2 readings were >95%. | From date and time of randomization to date and time of cessation of CPAP treatment, or until date and time of hospital discharge, if infant is on CPAP treatment until discharged (i.e., dies or is transferred), assessed to a maximum of 2 months of age. | 
| Surfactant Provided When FiO2 > 40% to Maintain SpO2 at 90-95% for ≥ 30 Minutes, With Respiratory Distress Syndrome Confirmed by Chest X-Ray | Surfactant provided when FiO2 > 40% to maintain SpO2 at 90-95% for ≥ 30 minutes, with Respiratory Distress Syndrome confirmed by chest X-Ray Note that endpoint likely corrupted because SpO2 was not routinely targeting 90-95%, and large number of infants received surfactant before achieving >40% or without having x-ray confirmation of RDS. | From date and time of randomization to date and time of cessation of CPAP treatment, or until date and time of hospital discharge, if infant is on CPAP treatment until discharged (i.e., dies or is transferred), assessed to a maximum of 2 months of age. | 
| CPAP Failure or Surfactant Provision | Outcomes 6 or 7 Note that endpoint likely corrupted because SpO2 was not routinely targeting 90-95%, and large number of infants received surfactant before achieving >40% or without having x-ray confirmation of RDS. | From date and time of randomization to date and time of cessation of CPAP treatment, or until date and time of hospital discharge, if infant is on CPAP treatment until discharged (i.e., dies or is transferred), assessed to a maximum of 2 months of age. | 
| CPAP Duration | Duration of CPAP treatment (hours) in infants that do not fail CPAP | From date and time of randomization to date and time of cessation of CPAP treatment, or until date and time of hospital discharge, if infant is on CPAP treatment until discharged (i.e., dies or is transferred), assessed to a maximum of 2 months of age. | 
| Serious Adverse Event | A Serious adverse Event (SAEs) is any untoward medial occurrence that: Results in death; Is life-threatening; [NOTE: the term life-threatening in the definition of serious refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe.] Requires inpatient hospitalisation or prolongation of existing hospitalisation; Results in persistent or significant disability/incapacity, or Is a congenital anomaly/birth defect | From date and time of birth to date and time of hospital discharge, assessed to a maximum of 2 months of age. | 
| Sentinel Outcome #1 | Damage to the nasal septum | From date and time of randomization to date and time of CPAP cessation, assessed to a maximum of 2 months of age. | 
| Sentinel Outcome #2 | Damage to the nares of the infant | From date and time of randomization to date and time of CPAP cessation, assessed to a maximum of 2 months of age. | 
| Sentinel Outcome #3 | Pneumothorax as diagnosed by X-ray | From date and time of randomization to date and time of CPAP cessation, assessed to a maximum of 2 months of age. | 
| Sentinel Outcome #4 | Intra-ventricular haemorrhage (IVH), intra-cranial haemorrhage (ICH), or periventricular leukomalacia (PVL) as diagnosed by cranial ultrasound scan | From date and time of randomization to date and time of CPAP cessation, assessed to a maximum of 2 months of age. | 
| Sentinel Outcome #5 | FiO2 ≥ 60% to maintain SpO2 at 90-95% for one hour or more, during CPAP treatment | From date and time of randomization to date and time of CPAP cessation, assessed to a maximum of 2 months of age. | 
| Sentinel Outcome #6 | Intubation and mechanical ventilation Note. An SpO2 target of 90-95% reflects currently recommended practice for neonates. FiO2 and SpO2 at time of intubation and ventilation not separately recorded, so we report this endpoint as recorded by clinicians, assuming that they have verified FiO2 [≥ 60% for ≥ 1 hour] and SpO2 [targeting 90-95%] requirements at the time of intubation and ventilation. If SpO2 was actually >95% (not 90-95%) at the time of intubation and ventilation, then FiO2 would be higher than required to meet the target range, by an unknown amount (possibly not meeting the FiO2 threshold of ≥ 60% for ≥ 1 hour, required to justify intubation and ventilation). We note this potential source of contamination because the results of Outcome #2 show that the majority of SpO2 readings were >95%. | From date and time of randomization to date and time of CPAP cessation, assessed to a maximum of 2 months of age. | 
| Sentinel Outcome #7 | For infants born at 28+0 to 33+6 weeks' gestation, oxygen dependent at 36 weeks' gestation | From date and time of randomization to date and time of CPAP cessation, assessed to a maximum of 2 months of age. | 
| Sentinel Outcome #8 | Death of the infant before hospitals discharge | From date and time of randomization to date and time of hospital discharge, assessed to a maximum of 2 months of age. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RDS