Trial Outcomes & Findings for Enteral L Citrulline Supplementation in Preterm Infants - Safety, Efficacy and Dosing (NCT NCT03649932)
NCT ID: NCT03649932
Last Updated: 2021-10-25
Results Overview
L-arginine and citrulline levels in the plasma will be measured via liquid chromatography-mass spectroscopy (LCMS) and a change (increase) in plasma levels of 20% on day 7 from baseline on day 0 will be considered significant.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
42 participants
Primary outcome timeframe
During the week of intervention (day 0 - day 7)
Results posted on
2021-10-25
Participant Flow
Participant milestones
| Measure |
Low Dose
50 mg/kg given two times a day (100 mg/kg/day) for total 7 days.
Enteral L-citrulline: L-Citrulline as 10 % solution (100 mg/ml) will be provided to the bedside nurse by the Investigational Pediatric Pharmacy. The drug will be given via gavage feeding by bolus infusions followed by a 0.5 ml water flush twice daily (0900 and 2100). Bolus dosing will be needed due to the small volumes (0.5-1.5 ml per dose in most infants). The volume of nasogastric tubing used in preterm infants (Ameritus 4.0 Fr 50 cm) is 0.48 ml, therefore we will follow the administration with 0.5 ml of saline/water flush to ensure all the study drug is delivered to the patient.
Administration of study drug - Will be given via gavage feeding tube twice daily (0900 +/- 30 mins, 2100 +/- 30 mins). L-citrulline will be given by the bedside nurse as a bolus followed by 0.5 ml water flush. L-citrulline will be given separate from feeds to avoid any confusion.
Study drug will be started when infant has been off of TPN for at least 3 days so that IV arginine in TPN does not interfere.
|
Medium Dose
100 mg/kg given two times a day (200 mg/kg/day) for total 7 days
Enteral L-citrulline: L-Citrulline as 10 % solution (100 mg/ml) will be provided to the bedside nurse by the Investigational Pediatric Pharmacy. The drug will be given via gavage feeding by bolus infusions followed by a 0.5 ml water flush twice daily (0900 and 2100). Bolus dosing will be needed due to the small volumes (0.5-1.5 ml per dose in most infants). The volume of nasogastric tubing used in preterm infants (Ameritus 4.0 Fr 50 cm) is 0.48 ml, therefore we will follow the administration with 0.5 ml of saline/water flush to ensure all the study drug is delivered to the patient.
Administration of study drug - Will be given via gavage feeding tube twice daily (0900 +/- 30 mins, 2100 +/- 30 mins). L-citrulline will be given by the bedside nurse as a bolus followed by 0.5 ml water flush. L-citrulline will be given separate from feeds to avoid any confusion.
Study drug will be started when infant has been off of TPN for at least 3 days so that IV arginine in TPN does not interfere.
|
High Dose
150 mg/kg given two times a day (300 mg/kg/day) for total 7 days.
Enteral L-citrulline: L-Citrulline as 10 % solution (100 mg/ml) will be provided to the bedside nurse by the Investigational Pediatric Pharmacy. The drug will be given via gavage feeding by bolus infusions followed by a 0.5 ml water flush twice daily (0900 and 2100). Bolus dosing will be needed due to the small volumes (0.5-1.5 ml per dose in most infants). The volume of nasogastric tubing used in preterm infants (Ameritus 4.0 Fr 50 cm) is 0.48 ml, therefore we will follow the administration with 0.5 ml of saline/water flush to ensure all the study drug is delivered to the patient.
Administration of study drug - Will be given via gavage feeding tube twice daily (0900 +/- 30 mins, 2100 +/- 30 mins). L-citrulline will be given by the bedside nurse as a bolus followed by 0.5 ml water flush. L-citrulline will be given separate from feeds to avoid any confusion.
Study drug will be started when infant has been off of TPN for at least 3 days so that IV arginine in TPN does not interfere.
|
|---|---|---|---|
|
Overall Study
STARTED
|
14
|
14
|
14
|
|
Overall Study
COMPLETED
|
14
|
13
|
13
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Enteral L Citrulline Supplementation in Preterm Infants - Safety, Efficacy and Dosing
Baseline characteristics by cohort
| Measure |
Low Dose
n=14 Participants
50 mg/kg given two times a day (100 mg/kg/day) for total 7 days.
Enteral L-citrulline: L-Citrulline as 10 % solution (100 mg/ml) will be provided to the bedside nurse by the Investigational Pediatric Pharmacy. The drug will be given via gavage feeding by bolus infusions followed by a 0.5 ml water flush twice daily (0900 and 2100). Bolus dosing will be needed due to the small volumes (0.5-1.5 ml per dose in most infants). The volume of nasogastric tubing used in preterm infants (Ameritus 4.0 Fr 50 cm) is 0.48 ml, therefore we will follow the administration with 0.5 ml of saline/water flush to ensure all the study drug is delivered to the patient.
Administration of study drug - Will be given via gavage feeding tube twice daily (0900 +/- 30 mins, 2100 +/- 30 mins). L-citrulline will be given by the bedside nurse as a bolus followed by 0.5 ml water flush. L-citrulline will be given separate from feeds to avoid any confusion.
Study drug will be started when infant has been off of TPN for at least 3 days so that IV arginine in TPN does not interfere.
|
Medium Dose
n=13 Participants
100 mg/kg given two times a day (200 mg/kg/day) for total 7 days
Enteral L-citrulline: L-Citrulline as 10 % solution (100 mg/ml) will be provided to the bedside nurse by the Investigational Pediatric Pharmacy. The drug will be given via gavage feeding by bolus infusions followed by a 0.5 ml water flush twice daily (0900 and 2100). Bolus dosing will be needed due to the small volumes (0.5-1.5 ml per dose in most infants). The volume of nasogastric tubing used in preterm infants (Ameritus 4.0 Fr 50 cm) is 0.48 ml, therefore we will follow the administration with 0.5 ml of saline/water flush to ensure all the study drug is delivered to the patient.
Administration of study drug - Will be given via gavage feeding tube twice daily (0900 +/- 30 mins, 2100 +/- 30 mins). L-citrulline will be given by the bedside nurse as a bolus followed by 0.5 ml water flush. L-citrulline will be given separate from feeds to avoid any confusion.
Study drug will be started when infant has been off of TPN for at least 3 days so that IV arginine in TPN does not interfere.
|
High Dose
n=13 Participants
150 mg/kg given two times a day (300 mg/kg/day) for total 7 days.
Enteral L-citrulline: L-Citrulline as 10 % solution (100 mg/ml) will be provided to the bedside nurse by the Investigational Pediatric Pharmacy. The drug will be given via gavage feeding by bolus infusions followed by a 0.5 ml water flush twice daily (0900 and 2100). Bolus dosing will be needed due to the small volumes (0.5-1.5 ml per dose in most infants). The volume of nasogastric tubing used in preterm infants (Ameritus 4.0 Fr 50 cm) is 0.48 ml, therefore we will follow the administration with 0.5 ml of saline/water flush to ensure all the study drug is delivered to the patient.
Administration of study drug - Will be given via gavage feeding tube twice daily (0900 +/- 30 mins, 2100 +/- 30 mins). L-citrulline will be given by the bedside nurse as a bolus followed by 0.5 ml water flush. L-citrulline will be given separate from feeds to avoid any confusion.
Study drug will be started when infant has been off of TPN for at least 3 days so that IV arginine in TPN does not interfere.
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
30 Weeks
STANDARD_DEVIATION 2.1 • n=5 Participants
|
29.6 Weeks
STANDARD_DEVIATION 2.5 • n=7 Participants
|
29 Weeks
STANDARD_DEVIATION 1.5 • n=5 Participants
|
29.4 Weeks
STANDARD_DEVIATION 2.1 • n=4 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
26 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
African American
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
|
Birth Weight
|
1125 grams
STANDARD_DEVIATION 383.5 • n=5 Participants
|
1272 grams
STANDARD_DEVIATION 460 • n=7 Participants
|
1250 grams
STANDARD_DEVIATION 350 • n=5 Participants
|
1250 grams
STANDARD_DEVIATION 393 • n=4 Participants
|
PRIMARY outcome
Timeframe: During the week of intervention (day 0 - day 7)L-arginine and citrulline levels in the plasma will be measured via liquid chromatography-mass spectroscopy (LCMS) and a change (increase) in plasma levels of 20% on day 7 from baseline on day 0 will be considered significant.
Outcome measures
| Measure |
Low Dose
n=14 Participants
50 mg/kg given two times a day (100 mg/kg/day) for total 7 days.
Enteral L-citrulline: L-Citrulline as 10 % solution (100 mg/ml) will be provided to the bedside nurse by the Investigational Pediatric Pharmacy. The drug will be given via gavage feeding by bolus infusions followed by a 0.5 ml water flush twice daily (0900 and 2100). Bolus dosing will be needed due to the small volumes (0.5-1.5 ml per dose in most infants). The volume of nasogastric tubing used in preterm infants (Ameritus 4.0 Fr 50 cm) is 0.48 ml, therefore we will follow the administration with 0.5 ml of saline/water flush to ensure all the study drug is delivered to the patient.
Administration of study drug - Will be given via gavage feeding tube twice daily (0900 +/- 30 mins, 2100 +/- 30 mins). L-citrulline will be given by the bedside nurse as a bolus followed by 0.5 ml water flush. L-citrulline will be given separate from feeds to avoid any confusion.
Study drug will be started when infant has been off of TPN for at least 3 days so that IV arginine in TPN does not interfere.
|
Medium Dose
n=13 Participants
100 mg/kg given two times a day (200 mg/kg/day) for total 7 days
Enteral L-citrulline: L-Citrulline as 10 % solution (100 mg/ml) will be provided to the bedside nurse by the Investigational Pediatric Pharmacy. The drug will be given via gavage feeding by bolus infusions followed by a 0.5 ml water flush twice daily (0900 and 2100). Bolus dosing will be needed due to the small volumes (0.5-1.5 ml per dose in most infants). The volume of nasogastric tubing used in preterm infants (Ameritus 4.0 Fr 50 cm) is 0.48 ml, therefore we will follow the administration with 0.5 ml of saline/water flush to ensure all the study drug is delivered to the patient.
Administration of study drug - Will be given via gavage feeding tube twice daily (0900 +/- 30 mins, 2100 +/- 30 mins). L-citrulline will be given by the bedside nurse as a bolus followed by 0.5 ml water flush. L-citrulline will be given separate from feeds to avoid any confusion.
Study drug will be started when infant has been off of TPN for at least 3 days so that IV arginine in TPN does not interfere.
|
High Dose
n=13 Participants
150 mg/kg given two times a day (300 mg/kg/day) for total 7 days.
Enteral L-citrulline: L-Citrulline as 10 % solution (100 mg/ml) will be provided to the bedside nurse by the Investigational Pediatric Pharmacy. The drug will be given via gavage feeding by bolus infusions followed by a 0.5 ml water flush twice daily (0900 and 2100). Bolus dosing will be needed due to the small volumes (0.5-1.5 ml per dose in most infants). The volume of nasogastric tubing used in preterm infants (Ameritus 4.0 Fr 50 cm) is 0.48 ml, therefore we will follow the administration with 0.5 ml of saline/water flush to ensure all the study drug is delivered to the patient.
Administration of study drug - Will be given via gavage feeding tube twice daily (0900 +/- 30 mins, 2100 +/- 30 mins). L-citrulline will be given by the bedside nurse as a bolus followed by 0.5 ml water flush. L-citrulline will be given separate from feeds to avoid any confusion.
Study drug will be started when infant has been off of TPN for at least 3 days so that IV arginine in TPN does not interfere.
|
|---|---|---|---|
|
Change in Plasma Levels of L-arginine and L-citrulline as Measured by LCMS Approach
Citrulline level (day 0)
|
24 micromol/L
Standard Deviation 9.5
|
33 micromol/L
Standard Deviation 17
|
26 micromol/L
Standard Deviation 11
|
|
Change in Plasma Levels of L-arginine and L-citrulline as Measured by LCMS Approach
Citrulline level (day 7)
|
112 micromol/L
Standard Deviation 85
|
150 micromol/L
Standard Deviation 89
|
171 micromol/L
Standard Deviation 139
|
|
Change in Plasma Levels of L-arginine and L-citrulline as Measured by LCMS Approach
Arginine level (day 0)
|
56 micromol/L
Standard Deviation 63
|
56 micromol/L
Standard Deviation 62
|
59 micromol/L
Standard Deviation 30
|
|
Change in Plasma Levels of L-arginine and L-citrulline as Measured by LCMS Approach
Arginine level (day 7)
|
91 micromol/L
Standard Deviation 63
|
134 micromol/L
Standard Deviation 62
|
162 micromol/L
Standard Deviation 67
|
PRIMARY outcome
Timeframe: During the week of intervention (day 0 - day 7)Measured by at least one adverse event that are determined to be related to the study drug.
Outcome measures
| Measure |
Low Dose
n=14 Participants
50 mg/kg given two times a day (100 mg/kg/day) for total 7 days.
Enteral L-citrulline: L-Citrulline as 10 % solution (100 mg/ml) will be provided to the bedside nurse by the Investigational Pediatric Pharmacy. The drug will be given via gavage feeding by bolus infusions followed by a 0.5 ml water flush twice daily (0900 and 2100). Bolus dosing will be needed due to the small volumes (0.5-1.5 ml per dose in most infants). The volume of nasogastric tubing used in preterm infants (Ameritus 4.0 Fr 50 cm) is 0.48 ml, therefore we will follow the administration with 0.5 ml of saline/water flush to ensure all the study drug is delivered to the patient.
Administration of study drug - Will be given via gavage feeding tube twice daily (0900 +/- 30 mins, 2100 +/- 30 mins). L-citrulline will be given by the bedside nurse as a bolus followed by 0.5 ml water flush. L-citrulline will be given separate from feeds to avoid any confusion.
Study drug will be started when infant has been off of TPN for at least 3 days so that IV arginine in TPN does not interfere.
|
Medium Dose
n=13 Participants
100 mg/kg given two times a day (200 mg/kg/day) for total 7 days
Enteral L-citrulline: L-Citrulline as 10 % solution (100 mg/ml) will be provided to the bedside nurse by the Investigational Pediatric Pharmacy. The drug will be given via gavage feeding by bolus infusions followed by a 0.5 ml water flush twice daily (0900 and 2100). Bolus dosing will be needed due to the small volumes (0.5-1.5 ml per dose in most infants). The volume of nasogastric tubing used in preterm infants (Ameritus 4.0 Fr 50 cm) is 0.48 ml, therefore we will follow the administration with 0.5 ml of saline/water flush to ensure all the study drug is delivered to the patient.
Administration of study drug - Will be given via gavage feeding tube twice daily (0900 +/- 30 mins, 2100 +/- 30 mins). L-citrulline will be given by the bedside nurse as a bolus followed by 0.5 ml water flush. L-citrulline will be given separate from feeds to avoid any confusion.
Study drug will be started when infant has been off of TPN for at least 3 days so that IV arginine in TPN does not interfere.
|
High Dose
n=13 Participants
150 mg/kg given two times a day (300 mg/kg/day) for total 7 days.
Enteral L-citrulline: L-Citrulline as 10 % solution (100 mg/ml) will be provided to the bedside nurse by the Investigational Pediatric Pharmacy. The drug will be given via gavage feeding by bolus infusions followed by a 0.5 ml water flush twice daily (0900 and 2100). Bolus dosing will be needed due to the small volumes (0.5-1.5 ml per dose in most infants). The volume of nasogastric tubing used in preterm infants (Ameritus 4.0 Fr 50 cm) is 0.48 ml, therefore we will follow the administration with 0.5 ml of saline/water flush to ensure all the study drug is delivered to the patient.
Administration of study drug - Will be given via gavage feeding tube twice daily (0900 +/- 30 mins, 2100 +/- 30 mins). L-citrulline will be given by the bedside nurse as a bolus followed by 0.5 ml water flush. L-citrulline will be given separate from feeds to avoid any confusion.
Study drug will be started when infant has been off of TPN for at least 3 days so that IV arginine in TPN does not interfere.
|
|---|---|---|---|
|
Safety of L-citrulline in Preterm Infants: Measured by at Least One Adverse Event
|
0 Number of Adverse Events
|
0 Number of Adverse Events
|
0 Number of Adverse Events
|
PRIMARY outcome
Timeframe: During the week of intervention (day 0 - day 7)Previous studies have shown that a plasma level of \> 37 micromol/L was effective in preventing pulmonary hypertension. This study sought to identify the dosing group of L-citrulline required to increase the plasma level of L-citrulline \> 37 micromol/L.
Outcome measures
| Measure |
Low Dose
n=10 Participants
50 mg/kg given two times a day (100 mg/kg/day) for total 7 days.
Enteral L-citrulline: L-Citrulline as 10 % solution (100 mg/ml) will be provided to the bedside nurse by the Investigational Pediatric Pharmacy. The drug will be given via gavage feeding by bolus infusions followed by a 0.5 ml water flush twice daily (0900 and 2100). Bolus dosing will be needed due to the small volumes (0.5-1.5 ml per dose in most infants). The volume of nasogastric tubing used in preterm infants (Ameritus 4.0 Fr 50 cm) is 0.48 ml, therefore we will follow the administration with 0.5 ml of saline/water flush to ensure all the study drug is delivered to the patient.
Administration of study drug - Will be given via gavage feeding tube twice daily (0900 +/- 30 mins, 2100 +/- 30 mins). L-citrulline will be given by the bedside nurse as a bolus followed by 0.5 ml water flush. L-citrulline will be given separate from feeds to avoid any confusion.
Study drug will be started when infant has been off of TPN for at least 3 days so that IV arginine in TPN does not interfere.
|
Medium Dose
n=11 Participants
100 mg/kg given two times a day (200 mg/kg/day) for total 7 days
Enteral L-citrulline: L-Citrulline as 10 % solution (100 mg/ml) will be provided to the bedside nurse by the Investigational Pediatric Pharmacy. The drug will be given via gavage feeding by bolus infusions followed by a 0.5 ml water flush twice daily (0900 and 2100). Bolus dosing will be needed due to the small volumes (0.5-1.5 ml per dose in most infants). The volume of nasogastric tubing used in preterm infants (Ameritus 4.0 Fr 50 cm) is 0.48 ml, therefore we will follow the administration with 0.5 ml of saline/water flush to ensure all the study drug is delivered to the patient.
Administration of study drug - Will be given via gavage feeding tube twice daily (0900 +/- 30 mins, 2100 +/- 30 mins). L-citrulline will be given by the bedside nurse as a bolus followed by 0.5 ml water flush. L-citrulline will be given separate from feeds to avoid any confusion.
Study drug will be started when infant has been off of TPN for at least 3 days so that IV arginine in TPN does not interfere.
|
High Dose
n=13 Participants
150 mg/kg given two times a day (300 mg/kg/day) for total 7 days.
Enteral L-citrulline: L-Citrulline as 10 % solution (100 mg/ml) will be provided to the bedside nurse by the Investigational Pediatric Pharmacy. The drug will be given via gavage feeding by bolus infusions followed by a 0.5 ml water flush twice daily (0900 and 2100). Bolus dosing will be needed due to the small volumes (0.5-1.5 ml per dose in most infants). The volume of nasogastric tubing used in preterm infants (Ameritus 4.0 Fr 50 cm) is 0.48 ml, therefore we will follow the administration with 0.5 ml of saline/water flush to ensure all the study drug is delivered to the patient.
Administration of study drug - Will be given via gavage feeding tube twice daily (0900 +/- 30 mins, 2100 +/- 30 mins). L-citrulline will be given by the bedside nurse as a bolus followed by 0.5 ml water flush. L-citrulline will be given separate from feeds to avoid any confusion.
Study drug will be started when infant has been off of TPN for at least 3 days so that IV arginine in TPN does not interfere.
|
|---|---|---|---|
|
Number of Participants With an Increase Plasma Level of L-citrulline > 37 Micromol/L
|
8 Participants
|
10 Participants
|
10 Participants
|
Adverse Events
Low Dose
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Medium Dose
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
High Dose
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place