Melatonin for Pulmonary Hypertension in Full Term Neonates

Phase 3

• Conditions: Neonatal Diseases and Abnormalities; Neonatal Mortality; Pulmonary Arterial Hypertension; Pulmonary Arterial Hypertension, Children
• Interventions: Drug: Melatonin; Other: Placebo

• Registration Number: NCT06685679
• Lead Sponsor: Ain Shams University

Brief Summary

Published evidence has provided a possible role of melatonin and the treatment of pulmonary hypertension through its strong antioxidant properties and improving vascular function in animals.

This study will test the hypothesis of the possible use of melatonin as an adjunct therapy to milrinone for neonatal pulmonary hypertension.

Detailed Description

Normal pulmonary artery pressure shows a gradual declining trend after birth, and pulmonary artery pressure of 72 h after birth is still higher than that of normal adults Infants born after 34 weeks of gestation with primary findings on physical examination reveals tachypnoea, retractions, grunting, desaturation unresponsive to supplemental O2, cyanosis and pulmonary arterial pressure (PAP) \> 25 mm Hg measured by echocardiography, within 72 h of birth, are considered to have pulmonary hypertension Pulmonary hypertension in neonates (PPHN) is a syndrome characterized by failure in the mechanisms that decrease pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP) after birth Persistent pulmonary hypertension of newborn (PPHN) develops when pulmonary vascular resistance (PVR) remains elevated after birth, resulting in right-to-left shunting of blood through fetal circulatory pathways. The PVR may remain elevated due to pulmonary hypoplasia, like that seen with congenital diaphragmatic hernia, and maladaptation of the pulmonary vascular bed as occurs with perinatal asphyxia It has been shown that one of the mechanisms involved in the pathophysiology of PPHN is oxidative stress, which results in an imbalance between an increase in free radicals generation and decreased antioxidant capacity Currently, the treatment for PHN considers timely and precise interventions such as intravenous milrinone, oral pulmonary vasodilators such as endothelin receptor antagonist, phosphodiesterase-5 inhibitors such as sildenafil, inhaled nitric oxideand are used both during acute and chronic phases of PPHN, controlled oxygen administration, and even extracorporeal membrane oxygenation.

However, these therapeutic strategies do not markedly reduce the mortality and the long-term neonatal outcomes remain poor Melatonin, more commonly known as the sleep hormone, has been highlighted by experimental evidence, to have significant effects as a direct scavenger of oxygen free radicals and induces antioxidant enzymatic It has been shown that melatonin has vasodilator properties and may modulate pro-oxidant sources in the neonatal lung which is proposed to treat PHN in the first days of neonatal life.

Study Timeline

• Study Start: 2024-05-15
• Status Verified: 2024-11
• Study First Submitted: 2024-11-11
• Study First Submitted QC: 2024-11-11
• Study First Posted: 2024-11-12
• Last Update Submitted: 2024-11-12
• Last Update Posted: 2024-11-13
• Primary Completion: 2024-12-15
• Study Completion: 2025-03-15

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• full term neonates ≥37 weeks diagnosed with pulmonary hypertension, with Pulmonary arterial pressure (PAP) > 25 mm Hg measured by echocardiography, within 72 h of birth (Chetan et al., 2022).

Exclusion Criteria

• Neonates with major congenital anomalies like congenital heart diseases

  • NPO or any contraindications to oral intake
  • Neonates with suspected inborn error of metabolism

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention group melatonin group	Melatonin	Intervention group : will receive oral melatonin (Kids Daily Vit Sleep syrup) 3 mg/kg/day divided in 3 doses , after enteral feeding, for 3 consecutive days, as combined therapy to milrinone (Garofoli et al., 2021). Human studies documented that short-term use of melatonin is safe, even in extreme doses (Andersen et al., 2016).
Control group	Placebo	Control group: will receive the treatment of PHN as our NICU protocol in the form of loading dose of milrinone (50 μg/kg) over 60 mins followed by a maintenance infusion (0.33-0.99 μg/kg/min) for 72 hrs. (McNamara et al., 2013) And equivalent amout of distilled water as a placebogive at same time intervals as melatoni

Primary Outcome Measures

Name	Time	Method
Pulmonary arterial pressure	After 72 hours of the start of the drug	Measuring pulmonary artery pressure by echocardiography
FiO2	Hourly for 3 days	FiO2 needs to maintain oxygen saturation monitored non invasively

Secondary Outcome Measures

Name	Time	Method
Hospital stay	One month	Duration of hospital stay

Trial Locations

Locations (1)

Ain shams university; 🇪🇬 Cairo, Egypt