Clinical Trial to Evaluate the Safety of Intravenous Paracetamol for Treatment of Patent Ductus Arteriosus in Preterm Infants

JRCT ID: jRCTs031220386

Registered date:17/10/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Patent Ductus Arteriosus in Preterm Infants
• Date of first enrollment: 17/10/2022
• Target sample size: 110
• Study type: Interventional

Intervention(s)

Intravenous Paracetamol Therapy
Paracetamol is administered at a dose of 15 mg/kg every 6 hours over 15 minutes, 4 times a day. Dosing should be continued for 3 consecutive days. If closure of the ductus arteriosus is achieved during intravenous acetaminophen therapy, the patient may be followed without further dosing. Acerio Intravenous 1000 mg is administered without dilution.

Outcome(s)

Primary Outcome

Incidence of renal dysfunction from the start of treatment to 48 hours after the end of treatment
Renal dysfunction: One of the following is met
1. Serum creatinine level: 0.3 mg/dL or 1.5-fold increase from baseline (screening period)
2. Urine output <1 mL/kg/H (24 hours)

Secondary Outcome

1. Percentage of ductus arteriosus closure at 24 hours after completion of study drug administration
2. Percentage of successful treatment (percentage of patients free from hemodynamically significant patent ductus arteriosus) at 24 hours after completion of study drug administration
3. Percentage of reopening of the ductus arteriosus between 24 and 48 hours after completion of study drug administration
4. Gastric and gastrointestinal bleeding from the start of the study drug administration to 48 hours after the end of the study drug administration
5. Perforation of stomach or gastrointestinal tract from the start of the study drug administration to 48 hours after the end of the study drug administration
6. Incidence of adverse drug reactions from the start of the study drug administration to 48 hours after the end of the study drug administration
7. Changes in the following laboratory values on the day of study drug administration start and 24 and 48 hours after the end of study drug administration
(1) Platelet count
(2) Serum urea nitrogen (BUN) level
(3) Serum creatinine (Cr) level
(4) Serum bilirubin (Bil) level
(5) Serum aspartate aminotransferase (AST) level
(6) Serum alanine aminotransferase (ALT) level
(7) Serum glucose level
(8) 24-hour urine output (mL/kg/H)
(9) Blood NTproBNP

Key inclusion & exclusion criteria

• Age minimum: >=
• Age maximum: <= 1weeks old
• Gender: Both

Include criteria

1. Newborn infants with a gestational age of at least 24 weeks but less than 35 weeks and birth weight of at least 500 g but less than 2,000 g
2. Newborn infants who can start receiving the study drug 24 hours to 7 days after birth
3. Newborn infants diagnosed with hemodynamically significant patent ductus arteriosus who meet both (1) and (2) below
(1) Left and right shunts
(2) One of the following
1) Arterial duct inner diameter > 1.5 mm
2) Left atrium to aorta ratio (LA/Ao) > 1.5
3) End-diastolic retrograde blood flow in the superior mesenteric artery or anterior cerebral artery
4. Newborn infants for whom written consent has been obtained from a surrogate

Exclude criteria

1. Newborn infants with a history of drug therapy for patent ductus arteriosus
(However, a small prophylactic dose of indomethacin for prevention of intraventricular hemorrhage is permitted.)
2. Newborn infants with a history of systemic administration of steroids within 24 hours of enrollment
3. Newborn infants with congenital heart disease (not including patent foramen ovale or left superior vena cava remnant)
4. Newborn infants with congenital malformation
5. Newborn infants with fetal hydrops
6. Newborn infants with a severe infection (positive blood culture at birth)
7. Newborn infants with pulmonary hypertension diagnosed by echocardiography (presence of foramen ovale or right-left shunt of ductus arteriosus)
8. Newborn infants with intraventricular hemorrhage (grade 3 or 4)
9. Newborn infants with hyperbilirubinemia requiring exchange transfusion
10. Newborn infants with necrotizing enterocolitis (Bell Classification 2 or 3)
11. Newborn infants with perforation of the stomach or gastrointestinal tract
12. Newborn infants with a bleeding tendency (hematuria, blood in tracheal aspirate, gastric aspirate, or stool, or persistent bleeding from the puncture site)
13. Newborn infants with a serum creatinine (Cr) level > 1.5 mg/dL during the screening period
14. Newborn infants with a urine output <1 mL/kg/H for 24 hours immediately before enrollment or <0.5 mL/kg/H for 24 hours after birth
15. Newborn infants with a platelet count <50,000/ul during the screening period
16. Newborn infants with an increase in ALT or AST of more than twice the normal value during the screening period.
(Normal values: ALT 6-50 U/L; AST 35-140 U/L)
17. Newborn infants who are judged to be ineligible for participation in this study by the principal investigator or a research associate.
(The laboratory values used to determine the exclusion criteria may be based on the results of tests performed prior to consent.)

Related Information

• Primary Sponsor: Namba Fumihiko
• Source(s) of Monetary Support: AMED BIRTHDAY