Pulmonary Hypertension Clinical Trial
Official title:
A Phase I, Safety and Pharmacokinetics/Pharmacodynamics Study of Oral L-CIT Supplementation in Preterm Infants With BPD±PH and NEC
NCT number | NCT05636397 |
Other study ID # | 1000077413 |
Secondary ID | |
Status | Recruiting |
Phase | N/A |
First received | |
Last updated | |
Start date | November 1, 2023 |
Est. completion date | March 2028 |
The purpose of this study is to evaluate the safety and explore the PK/PD of L-CIT supplementation in preterm infants to prevent the development of inflammatory pathways initiated by low levels of plasma CIT, specifically in preterm infants with post surgical NEC and BPD±PH.
Status | Recruiting |
Enrollment | 60 |
Est. completion date | March 2028 |
Est. primary completion date | December 2027 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 1 Month to 6 Months |
Eligibility | Arm 1: BPD±PH: Inclusion Criteria: - Born = 30 weeks at birth - Post-menstrual age (PMA) = 34 weeks - Echocardiographic evidence of PH for infants with BPD+PH - On invasive or non-invasive ventilation with RSS >2.0 for >12hours/day for at least 48 hours - Informed written consent (parents/substitute decision maker) Exclusion Criteria: - Congenital Heart Disease [Exceptions: small atrial septal defect (ASD), small ventricular septal defect (VSD), small patent ductus arteriosus (PDA)] - Infants with pulmonary vein stenosis - Concurrent sepsis with hemodynamic instability - Infants considered likely to die within next 7 days - Any other condition that, in the opinion of the investigator, may adversely affect the infant's ability to complete the study or its measures or pose significant risk to the infant. Arm 2: surgical NEC Inclusion Criteria - Born = 30 weeks at birth - Recovering from Stage IIIb NEC as per modified Bell's staging (pneumoperitoneum requiring surgery) - Tolerating 30 ml/kg/day of enteral feeds - On invasive or non-invasive ventilation (NIPPV/nCPAP) with RSS >2.0 for > 12hours/day for at least 48 hours, 10-14 days post surgery - Informed written consent (parents/substitute decision maker) - Considered medically stable by clinical team Exclusion Criteria: - Congenital heart disease (except small ASD, small VSD and non hsPDA) - Pulmonary vein stenosis - Concurrent sepsis with hemodynamic instability - Likely to die within next 7 days - Other condition significantly affecting pulmonary function independent of prematurity or NEC |
Country | Name | City | State |
---|---|---|---|
Canada | The Hospital For Sick Children | Toronto | Ontario |
Lead Sponsor | Collaborator |
---|---|
The Hospital for Sick Children |
Canada,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Safety of oral L-Citrulline administration | The number of patients with adverse events (AE) as a measure of safety and tolerability | 5 years | |
Secondary | Association of blood pressure as one of the PD outcomes with maximum L-CIT concentration (Cmax) | Blood pressure of the study participants will be associated with PK measures of L-CIT exposure i.e. Cmax using univariate correlation approaches. The investigator will then attempt to construct a PK/PD model to link PK and PD measures found to be of significance during the univariate screen. Future larger studies will then be used to examine these relationships with adequately powered studies. | 5 years | |
Secondary | Association of stoma or nasogastric output as one of the PD outcomes with maximum L-CIT concentration (Cmax) | Stoma or nasogastric output of the study participants will be associated with PK measures of L-CIT exposure i.e. Cmax using univariate correlation approaches. The investigator will then attempt to construct a PK/PD model to link PK and PD measures found to be of significance during the univariate screen. Future larger studies will then be used to examine these relationships with adequately powered studies. | 5 years | |
Secondary | Association of stool output as one of the PD outcomes with maximum L-CIT concentration (Cmax) | Stool output from the study participants will be associated with PK measures of L-CIT exposure i.e. Cmax using univariate correlation approaches. The investigator will then attempt to construct a PK/PD model to link PK and PD measures found to be of significance during the univariate screen. Future larger studies will then be used to examine these relationships with adequately powered studies. | 5 years | |
Secondary | Association of blood pressure with the area under the concentration time curve (AUC) for L-CIT | Blood pressure of the study participants will be associated with PK measures of L-CIT exposure i.e. Area under Concentration time curve (AUC) using univariate correlation approaches. The investigator will then attempt to construct a PK/PD model to link PK and PD measures found to be of significance during the univariate screen. | 5 years | |
Secondary | Association of stoma or nasogastric output with the area under the concentration time curve (AUC) for L-CIT | Stoma or nasogastric output of the study participants will be associated with PK measures of L-CIT exposure i.e. Area under Concentration time curve (AUC) using univariate correlation approaches. The investigator will then attempt to construct a PK/PD model to link PK and PD measures found to be of significance during the univariate screen. | 5 years | |
Secondary | Association of stool output with the area under the concentration time curve (AUC) for L-CIT | Stool output from the study participants will be associated with PK measures of L-CIT exposure i.e. Area under Concentration time curve (AUC) using univariate correlation approaches. The investigator will then attempt to construct a PK/PD model to link PK and PD measures found to be of significance during the univariate screen. | 5 years | |
Secondary | Association of blood pressure with minimum L-CIT concentration (Cmin) | Blood pressure of study participants will be associated with PK measures of L-CIT exposure i.e. Cmin using univariate correlation approaches. The investigator will then attempt to construct a PK/PD model to link PK and PD measures found to be of significance during the univariate screen. Future larger studies will then be used to examine these relationships with adequately powered studies. | 5 years | |
Secondary | Association of stoma or nasogastric output with minimum L-CIT concentration (Cmin) | Stoma or nasogastric output from study participants will be associated with PK measures of L-CIT exposure i.e. Cmin using univariate correlation approaches. The investigator will then attempt to construct a PK/PD model to link PK and PD measures found to be of significance during the univariate screen. Future larger studies will then be used to examine these relationships with adequately powered studies. | 5 years | |
Secondary | Association of stool output with minimum L-CIT concentration (Cmin) | Stool output from study participants will be associated with PK measures of L-CIT exposure i.e. Cmin using univariate correlation approaches. The investigator will then attempt to construct a PK/PD model to link PK and PD measures found to be of significance during the univariate screen. Future larger studies will then be used to examine these relationships with adequately powered studies. | 5 years | |
Secondary | Correlation between CIT and arginine levels | Correlation between changes in CIT and arginine levels with nitrite/nitrate levels | 5 years | |
Secondary | Biomarkers of inflammation | The levels of IL-1ß, IL-6, IL-8, IL-10, TNFa will be measured in tracheal aspirates and blood plasma. The aggregated levels fo these cytokines will reflect the inflammatory status of the study participant. | 5 years | |
Secondary | Oxidative stress | Oxidative stress (measured in tracheal aspirates and blood) | 5 years | |
Secondary | Respiratory Score (RSS) | The respiratory severity score (RSS) is a simplified severity score consisting of the mean airway pressure (MAP) multiplied by the fraction of inspired oxygen (FiO2). This score ranges from 0 to 12, with a higher score indicating more severe lung disease. | 5 years | |
Secondary | Desaturation index | The oxygen desaturation index (ODI) is commonly used to evaluate the severity of nocturnal hypoxemia. The ODI is defined as the number of episodes of oxygen desaturation per hour of sleep with desaturation events of >=10sec/ sampled hour. | 5 years | |
Secondary | Changes in Blood Pressure | Changes in diastolic and systolic blood pressure prior to and during CIT treatment. | 5 years | |
Secondary | Stoma, nasogastric or stool output | Volume of stoma, nasogastric or stool output prior to and during CIT treatment | 5 years | |
Secondary | Ventilation | Days on mechanical ventilation, non-invasive ventilation, and supplementary oxygen | 5 years | |
Secondary | BPD severity | Moderate to severe BPD based on the different mode of ventilatory support needed at 36 wks PMA.
No BPD = off all oxygen and positive pressure support Moderate BPD = low flow oxygen only Severe BPD= positive pressure support (high flow, CPAP, NIPPV, or ETT) |
5 years | |
Secondary | BPD | number of days of survival free of BPD | 5 years | |
Secondary | Pre-discharge mortality | Number of study participants who died during NICU admission. | 5 years | |
Secondary | Postnatal steroid Use | Number of days study participants received postnatal steroids during their NICU stay. | 5 years | |
Secondary | Bayley's scale for infant development | Bayley Scales of Infant and Toddler Development is an extensive formal developmental assessment tool for diagnosing developmental delays in early childhood. BSID is the commonly used abbreviation for Bayley Scales of Infant and Toddler Development. Bayley-III includes a motor score, and fine and gross motor subtest scores. The standardized mean motor score is 100 (SD 15), with scores lower than 85 indicating mild impairment, and lower than 70 indicating moderate or severe impairment.In this particular trial, the investigator would be looking at the correlation between the inflammatory markers (IL-1ß, IL-6, IL-8, IL-10, TNFa) and Neurodevelopmental outcomes from Bayley's scale during 18-24M follow up visit in babies received L-Citrulline during their NICU stay. | 5 years |
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