Trial Outcomes & Findings for Randomized Controlled Trial to Evaluate the Safety and Efficacy of Acetaminophen in Preterm Infants Used in Combination With Ibuprofen for Closure of the Ductus Arteriosus (NCT NCT03701074)

Results Overview

Ductal closure/constriction rate as defined based on the echocardiographic findings. Ductal closure/constriction will be defined as the complete closure of ductus or ductal diameter \<1 mm

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

1 participants

Primary outcome timeframe

24-48 hours after the completion of study intervention

Results posted on

2021-05-11

Participant Flow

Overall screening for the study enrollment started 12/15/2018. Screening was continued until 10/30/2020. The study was conducted at the Neonatal Intensive Care Unit

Participant milestones

Participant milestones
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Overall Study STARTED	1	0
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Overall Study Physician Decision	1	0

Baseline Characteristics

Randomized Controlled Trial to Evaluate the Safety and Efficacy of Acetaminophen in Preterm Infants Used in Combination With Ibuprofen for Closure of the Ductus Arteriosus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) n=1 Participants ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo	Total n=1 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Region of Enrollment United States	1 participants n=5 Participants	—	1 participants n=5 Participants
PDA size	1.5 mm n=5 Participants	—	1.5 mm n=5 Participants

PRIMARY outcome

Timeframe: 24-48 hours after the completion of study intervention

Population: None were enrolled for the control arm

Ductal closure/constriction rate as defined based on the echocardiographic findings. Ductal closure/constriction will be defined as the complete closure of ductus or ductal diameter \<1 mm

Outcome measures

Outcome measures
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) n=1 Participants ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Ductus Arteriosus Closure/Constriction Rate	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 24-48 hours after the completion of study intervention

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24-48 hours after the completion of study intervention

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24-48 hours after the completion of study intervention

liver enzymes before and after the study intervention

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24-48 hours after the completion of study intervention

Blood urea nitrogen (BUN) and serum creatinine before and after the study intervention

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24-48 hours after the completion of study intervention

Hematocrit and platelets before and after the study intervention

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at 36 weeks post menstrual age

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at discharge/40 weeks post menstrual age

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: until discharge/40 weeks post menstrual age

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from birth until discharge/40 weeks post menstrual age

Time to achieve 120 ml/kg/day of enteral feeding

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from birth until discharge/40 weeks post menstrual age

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from birth until discharge/40 weeks post menstrual age

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from birth until discharge/40 weeks post menstrual age

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from randomization until discharge/40 weeks post menstrual age

Outcome measures

Outcome data not reported

Adverse Events

Ibuprofen and Acetaminophen Arm (Intervention Arm)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 1 deaths

Ibuprofen and Placebo Arm (Control Arm)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Ibuprofen and Acetaminophen Arm (Intervention Arm) n=1 participants at risk ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Ibuprofen and acetaminophen: Intravenous ibuprofen given concomitantly with oral acetaminophen	Ibuprofen and Placebo Arm (Control Arm) ibuprofen and placebo will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Ibuprofen and placebo: Intravenous ibuprofen given concomitantly with oral placebo
Renal and urinary disorders Biochemical evidence of acute kidney injury with preserved renal function, probably nor related to i	100.0% 1/1 • 4 months None were enrolled into control arm, Therefore, number infants at risk for adverse events under the control arm are zero	— 0/0 • 4 months None were enrolled into control arm, Therefore, number infants at risk for adverse events under the control arm are zero

Additional Information

Ramachandra Bhat

University of South Alabama

Phone: 2514151055

Email: [email protected]; [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place