Ignite Creation Date:
2024-10-25 @ 7:58 PM
Last Modification Date:
2024-10-26 @ 3:37 PM
Study NCT ID:
NCT06552455
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-08
Brief Title:
Post-extubation Pressures in Preterm Neonates A CER Study
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Post-extubation Pressures on Non-invasive Respiratory Support in Preterm Neonates A Prospective Comparative Effectiveness Research Study
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The optimal post-extubation pressure level on non-invasive respiratory support modes - irrespective of the choice of the specific non-invasive mode - that optimizes extubation success and improves clinical outcomes remains unknown
The investigators aim to determine the optimal initial non-invasive pressure support level post-extubation in preterm neonates in relation to the pre-extubation measured mean airway pressures Paw The hypothesis is that use of higher pressures will lead to fewer re-intubations
This will be a prospective comparative effectiveness study across participating tertiary NICUs across Canada Centres will self-select whether to use Higher or EqualLower pressure levels as well as the initial post-extubation mode NIPPV or CPAP for the study duration Only the first eligible extubation will be included for analysis Eligible patients 28 weeks gestational age at birth undergoing an eligible extubation from a mean airway pressure 13 cmH2O will be included The primary outcome will be re-intubation within 7 days Secondary outcomes will include other neonatal morbidities
The investigators aim to determine the optimal initial non-invasive pressure support level post-extubation in preterm neonates in relation to the pre-extubation measured mean airway pressures Paw The hypothesis is that use of higher pressures will lead to fewer re-intubations
This will be a prospective comparative effectiveness study across participating tertiary NICUs across Canada Centres will self-select whether to use Higher or EqualLower pressure levels as well as the initial post-extubation mode NIPPV or CPAP for the study duration Only the first eligible extubation will be included for analysis Eligible patients 28 weeks gestational age at birth undergoing an eligible extubation from a mean airway pressure 13 cmH2O will be included The primary outcome will be re-intubation within 7 days Secondary outcomes will include other neonatal morbidities
Detailed Description:
BACKGROUND Invasive mechanical ventilation IMV is a well-established risk factor for bronchopulmonary dysplasia and associated long-term complications In recent years a large body of research has evaluated and helped establish clinical practices aimed at avoiding initiation of IMV altogether by using non-invasive respiratory support modes such as CPAP in place of routine intubation and use of minimally invasive surfactant treatment Despite such efforts 85 of preterm neonates 280 weeks gestational age require IMV Canadian Neonatal Network data - unpublished Furthermore 25 of preterm neonates extubated to non-invasive support ultimately require re-intubation Canadian Neonatal Network data - unpublished which itself is associated with complications including mortality and bronchopulmonary dysplasia As such further research on strategies to facilitate successful extubation is required While there has been a considerable focus on comparing various modes of non-invasive support following extubation there are limited published data on peri-extubation practices particularly as they relate to the choice of post-extubation pressure levels
In the meantime there is considerable practice variability in choice of initial settings on both CPAP and NIPPV A national-level survey unpublished demonstrated an almost even split - with half the sites choosing equal or lower pressures whereas others choosing slightly higher pressures on the initial non-invasive respiratory support compared to pre-extubation pressures on IMV As such while the optimal post-extubation pressure level on non-invasive respiratory support that optimizes extubation success and clinical outcomes remains unknown this natural practical variability affords a unique opportunity to conduct this comparative effectiveness research study using real-world data
OBJECTIVE To determine the optimal initial non-invasive respiratory pressure support level following extubation in preterm neonates
HYPOTHESIS The hypothesis is that higher pressures will lead to fewer re-intubations
SPECIFIC RESEARCH QUESTION
Population Preterm neonates GA 28 weeks gestation admitted to a participating centre who received any duration of mechanical ventilation
Patient-level exclusion criteria
Major chromosomalgeneticcongenital abnormalities Never received invasive mechanical ventilation IMV Received IMV but never extubated to non-invasive respiratory support NRS Transferred to non-participating site while intubated Death prior to extubation Initial extubation was for withdrawal of care
Lack of any eligible extubation defined as ALL of the following
i 36 continuous hours on IMV ii pre-extubation MAP 13 cmH2O and iii on post-extubation NRS for 1 hour
Intervention group Higher Pressure
Control groups EqualLower Pressure
Primary outcome
1 Re-intubation within 7 days
Secondary outcomes
2 Failure of initial NRS within 7 days defined as any escalation beyond originally assigned settings escalation to an alternate NRS mode andor re-intubation
3 Presence of any one or more pre-defined re-intubation criteria within 7 days
4 Moderate-severe bronchopulmonary dysplasia
5 Death any cause prior to discharge
6 Death any cause prior to discharge OR moderate-severe bronchopulmonary dysplasia
7 Post-extubation days on any form of positive pressure respiratory support
8 Post-extubation days on invasive mechanical ventilation
9 New pulmonary air leak including pneumothorax pulmonary interstitial emphysema andor pneumo-mediastinum within 7 days of extubation per radiology report
10 New gastro-intestinal perforation any cause within 7 days of extubation per radiology report
11 Necrotizing enterocolitis diagnosed any time post-extubation
METHODS
This will be a prospective comparative effectiveness research study based on real-world practices across participating tertiary NICUs in Canada Centres have self-selected or in cases where there is no preference assigned
1 Intervention Higher pressure vs control arm EqualLower pressure pressure levels as the initial post-extubation pressure level and
2 CPAP vs NIPPV as the initial post-extubation mode
Note Biphasic CPAP and Non-invasive high frequency ventilation NIHFV will be considered sub-forms of CPAP whereas non-invasive neurally adjusted ventilatory assist NIV-NAVA will be considered a sub-form of NIPPV
Only the first eligible extubation will be included for analyses however it will be recommended that centres follow their assigned strategy for all eligible extubations
Peri-extubation respiratory management
Pre-extubation Among eligible babies 28 weeks GA the first extubation from any ventilator mode that meets all of the following criteria will be included
1 Extubation after 36 continuous hours of IMV
2 Measured pre-extubation Paw 13 cmH2O
3 NOT re-intubated within 1 hour of extubation
The decision and timing of extubation will rest completely with the medical team specific extubation criteria will NOT be mandated Data on actual pre-extubation modes and settings will be collected the pre-extubation mean airway pressure Paw will be determined based on the measured value as provided by the ventilator prior to extubation
Extubation procedure The extubation procedure will be as per each individual centres respective standard practice Once the nasal interface is applied the stipulated mode and NRS pressures should be in effect immediately and the initial post-extubation mode and settings will be documented by the bedside healthcare provider
Post-extubation Any device capable of generating the stipulated pressures may be used however only short binasal prongs andor nasal mask interfaces will be permitted as the initial interface for the 1st 6 hours post-extubation
Centres in the Higher NRS pressures arm will be required to maintain the stipulated NRS pressures as a minimum for at least 6 hours a consensus-based choice of duration that will allow for sufficient stabilization of the lungs while avoiding premature weaning Any wean within the first 6 hours will be considered a protocol deviation and the reason for the wean will be documented Pressure escalations will be permitted based on patient-need at clinicians discretion as well as escalation to alternate modes andor intubation as needed All other respiratory management will be as per the medical team
Centres in the EqualLower NRS pressures arm will choose initial pressures as stipulated based on pre-extubation pressures All subsequent management will be as per the medical team
Re-intubation criteria Suggested minimum re-intubation criteria will be provided if non-invasive support despite escalation of pressure levels andor use of rescue modes based on clinical teams discretion is deemed insufficient While these criteria will not be strictly enforced patient records will be reviewed to identify patients who meet these criteria over 1st 7 days one of the secondary outcomes
Statistical Analyses
The primary analyses will be conducted by first classifying patients based on treatment provided as-treated classification As such each patient will be classified into Higher NRS pressures or EqualLower NRS pressures regardless of the centre based on the initial post-extubation strategy employed Patients extubated to a strategy different than either of the two stipulated ones eg extubation to Paw 3 cmH2O or extubation directly to room air will be excluded from these analyses
Demographics and baseline data will be summarized using appropriate univariate analyses - Chi-squared or Fishers exact test for categorical variables and T-test or Wilcoxon Rank Sum test for continuous variables
Centre characteristics will be descriptively summarized grouped by study arm Outcomes analyses - unadjusted All outcomes will be summarized based on treatment provided and described using appropriate univariate analyses Unadjusted odds ratios and unadjusted meanmedian differences with 95 confidence intervals will be reported for categorical and continuous variables respectively
Outcomes analyses - adjusted The investiagtors will conduct multivariable logistic and linear regression models for the primary and all secondary outcomes These analyses will yield adjusted odds ratios or adjusted mean differences with 95 confidence intervals for categorical and continuous outcomes respectively Covariates for adjusted analyses - Adjusted modes for all outcomes will include the following three variables regardless of the P values from univariate analyses due to their biological relevance and importance to all outcomes gestational age sex and the initial post-extubation NRS mode ie CPAP or NIPPV The following baseline and demographic variables will be considered for inclusion as covariates in the model for the primary outcome antenatal steroids hypertensive disorder of pregnancy small for gestational age 10ile multiple pregnancy out-born status ie delivered at a non-tertiary care centre cesarian section score for neonatal acute physiology SNAP multiple doses of surfactant chronological age at extubation administration of post-natal steroids at time of extubation sepsis or meningitis or necrotizing enterocolitis any time prior to extubation FiO2 pre-extubation and pre-extubation Paw These variables have been considered based on the available literature on clinical predictors of extubation failure and biologicalclinical rationale However only those variables with a P value 020 a conservative cut-off based on univariate analyses will be included in the model Furthermore we will check for multi-collinearity amongst included variables to ensure avoidance of over-adjustment by monitoring the variance inflation factor utilizing a cut-off value of 50 Finally to account for centre-specific differences ie clustering within centres a generalized estimating equations approach will be used for all models with an appropriate covariance structure
Note The baselinedemographic variables under consideration as co-variates in models for the secondary outcomes will be similar to that for the primary outcome
Sample Size
Recent national-level data gathered for a previous similar comparative effectiveness research study contains data on re-intubation risk in neonates 28 weeks gestation the population of interest in this proposal While this data does not account for post-extubation NRS settings is it estimated that for patients extubated to EqualLower NRS pressures the re-intubation risk will be 25 In a recent unpublished survey 86 of knowledge users across Canada responded that a 75 absolute risk reduction in re-intubation would be likely or very likely to change their clinical practice To demonstrate this 75 absolute risk reduction ie a re-intubation risk of 175 with use of Higher NRS pressures will require a minimum of 367 patients in each arm one-sided α of 005 and β of 020 from Pearson Chi-square test or Likelihood ratio test As such over a planned 35-year study recruitment period allowing for up to 30 loss in eligibility eg transfer to a non-participating centre while still on IMV extubation for withdrawal of life-sustaining therapy or extubation to an NRS modesettings not part of the study at least 525 patients will be recruited in both groups ie total sample size 1050 This will be the largest and adequately powered study to address this important question faced on a day-to-day basis by healthcare providers caring for preterm neonates
Planned Sensitivity Analyses
The investigators will conduct the following sensitivity analyses for the primary outcome only
1 Intention-to-treat analysis In accordance with the EQUATOR network guidelines patients will be classified to Higher vs EqualLower NRS pressures based on the centre-assignment irrespective of actual modes or pressures utilized This will include patients who were extubated to a strategy not part of the study Remaining analyses will be similar to as described earlier for the primary as-treated cohort
2 Per-protocol analysis Patients will be classified based on centre-assignment AND limited to only those infants who received the intended post-extubation NRS pressures For example from a centre that has self-selected to Higher NRS only patients extubated to Higher NRS levels on CPAP or NIPPV will be included Remaining analyses will be similar to as described earlier for the primary as-treated cohort
3 Propensity-score matched analysis will be conducted to assess the accuracy of the primary analyses Propensity-score matched analyses are considered more robust than traditional regression models in certain situations especially when confounding by indication is suspected In this model each patient is assigned a probability propensity-score of receiving the assigned treatment ie Higher vs EqualLower NRS based on the distribution of baseline and demographic variables that precede the treatment using a regression model It is assumed that subjects with the same propensity score have a similar distribution of observed covariates independent of the treatment received We will confirm that the estimated propensity score balances covariates by regressing each covariate on treatment For any unbalanced covariates the model will be updated by allowing for effect modification including covariate interactions and non-linearity including higher powers of continuous covariates until all covariates are balanced The propensity scores will then be used to match subjects with similar probabilities of receiving one of the two treatment strategies Matching will be performed using the SAS macro matchsas SAS Institute Inc Cary NC USA based on a caliper width of 02 times the standard deviation of the logit-transformed propensity score Overall this analysis is expected to create a cohort that approximates that of a traditional randomized controlled trial
Planned Subgroup Analyses
Subgroup analyses will be conducted for the following for the primary outcome only
1 Patients extubated to CPAP ie comparison of Higher vs EqualLower CPAP excluding BiPhasic CPAP and NIHFV and patients extubated to NIPPV ie comparison of Higher vs EqualLower NIPPV excluding NIV-NAVA
2 Chronological age at extubation 14 days ie comparison of Higher vs EqualLower NRS in babies extubated at age 14 days and chronological age at extubation 14 days ie comparison of Higher vs EqualLower NRS in neonates extubated at age 14 days
3 GA at birth 26 weeks ie comparison of Higher vs EqualLower NRS in babies born at 26 weeks and GA at birth 26 weeks ie comparison of Higher vs EqualLower NRS in babies born at 26 weeks
Both sets of subgroup analyses will follow a similar analytical plan as the primary analyses including similar covariates for each outcome as long as P-value and multicollinearity conditions are met
In the meantime there is considerable practice variability in choice of initial settings on both CPAP and NIPPV A national-level survey unpublished demonstrated an almost even split - with half the sites choosing equal or lower pressures whereas others choosing slightly higher pressures on the initial non-invasive respiratory support compared to pre-extubation pressures on IMV As such while the optimal post-extubation pressure level on non-invasive respiratory support that optimizes extubation success and clinical outcomes remains unknown this natural practical variability affords a unique opportunity to conduct this comparative effectiveness research study using real-world data
OBJECTIVE To determine the optimal initial non-invasive respiratory pressure support level following extubation in preterm neonates
HYPOTHESIS The hypothesis is that higher pressures will lead to fewer re-intubations
SPECIFIC RESEARCH QUESTION
Population Preterm neonates GA 28 weeks gestation admitted to a participating centre who received any duration of mechanical ventilation
Patient-level exclusion criteria
Major chromosomalgeneticcongenital abnormalities Never received invasive mechanical ventilation IMV Received IMV but never extubated to non-invasive respiratory support NRS Transferred to non-participating site while intubated Death prior to extubation Initial extubation was for withdrawal of care
Lack of any eligible extubation defined as ALL of the following
i 36 continuous hours on IMV ii pre-extubation MAP 13 cmH2O and iii on post-extubation NRS for 1 hour
Intervention group Higher Pressure
Control groups EqualLower Pressure
Primary outcome
1 Re-intubation within 7 days
Secondary outcomes
2 Failure of initial NRS within 7 days defined as any escalation beyond originally assigned settings escalation to an alternate NRS mode andor re-intubation
3 Presence of any one or more pre-defined re-intubation criteria within 7 days
4 Moderate-severe bronchopulmonary dysplasia
5 Death any cause prior to discharge
6 Death any cause prior to discharge OR moderate-severe bronchopulmonary dysplasia
7 Post-extubation days on any form of positive pressure respiratory support
8 Post-extubation days on invasive mechanical ventilation
9 New pulmonary air leak including pneumothorax pulmonary interstitial emphysema andor pneumo-mediastinum within 7 days of extubation per radiology report
10 New gastro-intestinal perforation any cause within 7 days of extubation per radiology report
11 Necrotizing enterocolitis diagnosed any time post-extubation
METHODS
This will be a prospective comparative effectiveness research study based on real-world practices across participating tertiary NICUs in Canada Centres have self-selected or in cases where there is no preference assigned
1 Intervention Higher pressure vs control arm EqualLower pressure pressure levels as the initial post-extubation pressure level and
2 CPAP vs NIPPV as the initial post-extubation mode
Note Biphasic CPAP and Non-invasive high frequency ventilation NIHFV will be considered sub-forms of CPAP whereas non-invasive neurally adjusted ventilatory assist NIV-NAVA will be considered a sub-form of NIPPV
Only the first eligible extubation will be included for analyses however it will be recommended that centres follow their assigned strategy for all eligible extubations
Peri-extubation respiratory management
Pre-extubation Among eligible babies 28 weeks GA the first extubation from any ventilator mode that meets all of the following criteria will be included
1 Extubation after 36 continuous hours of IMV
2 Measured pre-extubation Paw 13 cmH2O
3 NOT re-intubated within 1 hour of extubation
The decision and timing of extubation will rest completely with the medical team specific extubation criteria will NOT be mandated Data on actual pre-extubation modes and settings will be collected the pre-extubation mean airway pressure Paw will be determined based on the measured value as provided by the ventilator prior to extubation
Extubation procedure The extubation procedure will be as per each individual centres respective standard practice Once the nasal interface is applied the stipulated mode and NRS pressures should be in effect immediately and the initial post-extubation mode and settings will be documented by the bedside healthcare provider
Post-extubation Any device capable of generating the stipulated pressures may be used however only short binasal prongs andor nasal mask interfaces will be permitted as the initial interface for the 1st 6 hours post-extubation
Centres in the Higher NRS pressures arm will be required to maintain the stipulated NRS pressures as a minimum for at least 6 hours a consensus-based choice of duration that will allow for sufficient stabilization of the lungs while avoiding premature weaning Any wean within the first 6 hours will be considered a protocol deviation and the reason for the wean will be documented Pressure escalations will be permitted based on patient-need at clinicians discretion as well as escalation to alternate modes andor intubation as needed All other respiratory management will be as per the medical team
Centres in the EqualLower NRS pressures arm will choose initial pressures as stipulated based on pre-extubation pressures All subsequent management will be as per the medical team
Re-intubation criteria Suggested minimum re-intubation criteria will be provided if non-invasive support despite escalation of pressure levels andor use of rescue modes based on clinical teams discretion is deemed insufficient While these criteria will not be strictly enforced patient records will be reviewed to identify patients who meet these criteria over 1st 7 days one of the secondary outcomes
Statistical Analyses
The primary analyses will be conducted by first classifying patients based on treatment provided as-treated classification As such each patient will be classified into Higher NRS pressures or EqualLower NRS pressures regardless of the centre based on the initial post-extubation strategy employed Patients extubated to a strategy different than either of the two stipulated ones eg extubation to Paw 3 cmH2O or extubation directly to room air will be excluded from these analyses
Demographics and baseline data will be summarized using appropriate univariate analyses - Chi-squared or Fishers exact test for categorical variables and T-test or Wilcoxon Rank Sum test for continuous variables
Centre characteristics will be descriptively summarized grouped by study arm Outcomes analyses - unadjusted All outcomes will be summarized based on treatment provided and described using appropriate univariate analyses Unadjusted odds ratios and unadjusted meanmedian differences with 95 confidence intervals will be reported for categorical and continuous variables respectively
Outcomes analyses - adjusted The investiagtors will conduct multivariable logistic and linear regression models for the primary and all secondary outcomes These analyses will yield adjusted odds ratios or adjusted mean differences with 95 confidence intervals for categorical and continuous outcomes respectively Covariates for adjusted analyses - Adjusted modes for all outcomes will include the following three variables regardless of the P values from univariate analyses due to their biological relevance and importance to all outcomes gestational age sex and the initial post-extubation NRS mode ie CPAP or NIPPV The following baseline and demographic variables will be considered for inclusion as covariates in the model for the primary outcome antenatal steroids hypertensive disorder of pregnancy small for gestational age 10ile multiple pregnancy out-born status ie delivered at a non-tertiary care centre cesarian section score for neonatal acute physiology SNAP multiple doses of surfactant chronological age at extubation administration of post-natal steroids at time of extubation sepsis or meningitis or necrotizing enterocolitis any time prior to extubation FiO2 pre-extubation and pre-extubation Paw These variables have been considered based on the available literature on clinical predictors of extubation failure and biologicalclinical rationale However only those variables with a P value 020 a conservative cut-off based on univariate analyses will be included in the model Furthermore we will check for multi-collinearity amongst included variables to ensure avoidance of over-adjustment by monitoring the variance inflation factor utilizing a cut-off value of 50 Finally to account for centre-specific differences ie clustering within centres a generalized estimating equations approach will be used for all models with an appropriate covariance structure
Note The baselinedemographic variables under consideration as co-variates in models for the secondary outcomes will be similar to that for the primary outcome
Sample Size
Recent national-level data gathered for a previous similar comparative effectiveness research study contains data on re-intubation risk in neonates 28 weeks gestation the population of interest in this proposal While this data does not account for post-extubation NRS settings is it estimated that for patients extubated to EqualLower NRS pressures the re-intubation risk will be 25 In a recent unpublished survey 86 of knowledge users across Canada responded that a 75 absolute risk reduction in re-intubation would be likely or very likely to change their clinical practice To demonstrate this 75 absolute risk reduction ie a re-intubation risk of 175 with use of Higher NRS pressures will require a minimum of 367 patients in each arm one-sided α of 005 and β of 020 from Pearson Chi-square test or Likelihood ratio test As such over a planned 35-year study recruitment period allowing for up to 30 loss in eligibility eg transfer to a non-participating centre while still on IMV extubation for withdrawal of life-sustaining therapy or extubation to an NRS modesettings not part of the study at least 525 patients will be recruited in both groups ie total sample size 1050 This will be the largest and adequately powered study to address this important question faced on a day-to-day basis by healthcare providers caring for preterm neonates
Planned Sensitivity Analyses
The investigators will conduct the following sensitivity analyses for the primary outcome only
1 Intention-to-treat analysis In accordance with the EQUATOR network guidelines patients will be classified to Higher vs EqualLower NRS pressures based on the centre-assignment irrespective of actual modes or pressures utilized This will include patients who were extubated to a strategy not part of the study Remaining analyses will be similar to as described earlier for the primary as-treated cohort
2 Per-protocol analysis Patients will be classified based on centre-assignment AND limited to only those infants who received the intended post-extubation NRS pressures For example from a centre that has self-selected to Higher NRS only patients extubated to Higher NRS levels on CPAP or NIPPV will be included Remaining analyses will be similar to as described earlier for the primary as-treated cohort
3 Propensity-score matched analysis will be conducted to assess the accuracy of the primary analyses Propensity-score matched analyses are considered more robust than traditional regression models in certain situations especially when confounding by indication is suspected In this model each patient is assigned a probability propensity-score of receiving the assigned treatment ie Higher vs EqualLower NRS based on the distribution of baseline and demographic variables that precede the treatment using a regression model It is assumed that subjects with the same propensity score have a similar distribution of observed covariates independent of the treatment received We will confirm that the estimated propensity score balances covariates by regressing each covariate on treatment For any unbalanced covariates the model will be updated by allowing for effect modification including covariate interactions and non-linearity including higher powers of continuous covariates until all covariates are balanced The propensity scores will then be used to match subjects with similar probabilities of receiving one of the two treatment strategies Matching will be performed using the SAS macro matchsas SAS Institute Inc Cary NC USA based on a caliper width of 02 times the standard deviation of the logit-transformed propensity score Overall this analysis is expected to create a cohort that approximates that of a traditional randomized controlled trial
Planned Subgroup Analyses
Subgroup analyses will be conducted for the following for the primary outcome only
1 Patients extubated to CPAP ie comparison of Higher vs EqualLower CPAP excluding BiPhasic CPAP and NIHFV and patients extubated to NIPPV ie comparison of Higher vs EqualLower NIPPV excluding NIV-NAVA
2 Chronological age at extubation 14 days ie comparison of Higher vs EqualLower NRS in babies extubated at age 14 days and chronological age at extubation 14 days ie comparison of Higher vs EqualLower NRS in neonates extubated at age 14 days
3 GA at birth 26 weeks ie comparison of Higher vs EqualLower NRS in babies born at 26 weeks and GA at birth 26 weeks ie comparison of Higher vs EqualLower NRS in babies born at 26 weeks
Both sets of subgroup analyses will follow a similar analytical plan as the primary analyses including similar covariates for each outcome as long as P-value and multicollinearity conditions are met
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None