Paracetamol Treatment of the Borderline Significant PDA

Shaare Zedek Medical Center

Status and phase: Unknown; Phase 2

Conditions: Patent Ductus Arteriosus

Treatments: Drug: Paracetamol drops; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02819414

0174-16-SZMC

Details and patient eligibility

About

The therapeutic approach to the patent ductus arteriosus (PDA) in the premature neonate remains controversial. Currently it is generally accepted to treat only hemodynamically significant PDAs. The current investigation aims to study the effect of treatment on PDAs of borderline significance via a prospective, randomized controlled trial of paracetamol in this group.

Full description

In the neonatal intensive care unit of the Shaare Zedek Medical Center, preterm babies <30 wks. GA, are studied echocardiographically on day of life 3-4. Pending parental informed consent, those diagnosed with a PDA of borderline significance will be randomized to receive either paracetamol or placebo for three days, followed by a repeat echocardiogram. If the PDA remains of borderline significance, the treatment will be continued for an additional 4 days (1 week total). Paracetamol levels and liver functions will be assessed after the third day. Babies will be followed until discharge for subsequent PDA pathology; respiratory distress and chronic lung disease [CLD]; necrotizing enterocolitis [NEC]; retinopathy of prematurity [ROP].

The investigators' primary goal is to demonstrate a decrease in the composite outcome of death or severe morbidity chronic lung disease [CLD], as shown by decreased time on supplemental oxygen and assisted ventilation.

Secondary goals:

• To demonstrate a decrease in subsequently diagnosed hs PDA, including

  • Decrease in the need for subsequent therapy for PDA closure
  • Decrease in surgical PDA ligations

• To demonstrate a decrease in necrotizing enterocolitis (NEC) and/or ROP with treatment.

• To demonstrate no adverse effect on blood flow in anterior cerebral, superior mesenteric and renal arteries.

Enrollment: 80 estimated patients

Sex: All

Ages: 3 to 6 days old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Preterm neonates < 30 weeks' gestational age PDA of borderline significance

Exclusion criteria

• Infants not deemed likely to survive more than one week Infants with congenital heart malformations Infants with pulmonary hypertension and right to left ductal shunting

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

80 participants in 2 patient groups, including a placebo group

Control Group

Placebo Comparator group

Description:

Treatment with placebo at a volume of 2.25 cc/kg/dose x 4/day to be given with feeds, or in place of feed when baby is receiving \<2 cc/kg/feed.

Treatment:

Other: Placebo

Treatment Group

Active Comparator group

Description:

Treatment with paracetamol drops at 15 mg/kg/dose x 4/day. Drops will be diluted 1:15 in order to reduce osmolality. This will yield a dose of 2.25 ml/kg/dose, to be given with feeds, or in place of feed when baby is receiving \<2 cc/kg/feed.

Treatment:

Drug: Paracetamol drops