Clinical trial NCT06685679: Melatonin for Pulmonary Hypertension in Full Term Neonates
Official title: Melatonin As an Adjunct Therapy to Milrinone for Pulmonary Hypertension in Full Term Neonates
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Neonatal Diseases and Abnormalities
Neonatal Mortality
Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension, Children
Keywords: Neonate
Pulmonary hypertension
Melatonin
Milrinon
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2024-11-12
Enrollment: 40
Sex: ALL
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pulmonary arterial pressure
timeFrame: After 72 hours of the start of the drug
measure: FiO2
timeFrame: Hourly for 3 days
Secondary outcomes:
measure: Hospital stay
timeFrame: One month
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Ain shams university
Study officials:
References:
citation: Chetan C, Suryawanshi P, Patnaik S, Soni NB, Rath C, Pareek P, Gupta B, Garegrat R, Verma A, Singh Y. Oral versus intravenous sildenafil for pulmonary hypertension in neonates: a randomized trial. BMC Pediatr. 2022 May 27;22(1):311. doi: 10.1186/s12887-022-03366-3.
citation: 1- Andersen LPH., Gögenur I, Rosenberg J, Reiter RJ. The safety of melatonin in humans. Clin Drug Investig. 2016 Mar. 36(3), 169-175. 2- Ballard JL, Khoury JC, Wedig K, Wang L, Eilers-Walsman BL and Lipp R. New Ballard Score, expanded to include extremely premature infants. J pediatr. 1991 sep. 119(3), 417-423. 3- Chetan C, Suryawanshi P, Patnaik S, Soni NB, Rath C, Pareek P,et al. Oral versus intravenous sildenafil for pulmonary hypertension in neonates: a randomized trial. BMC pediatr . 2022 May . 22(1), 1-7. 4- D'Angelo, G., Chimenz, R., Reiter, R. J., & Gitto, E. Use of melatonin in oxidative stress related neonatal diseases. Antioxidants. 2020, 9(6), 477