Neonatal Diseases and AbnormalitiesPhase 3NCT06685679
Melatonin for Pulmonary Hypertension in Full Term Neonates
A Phase 3 study testing Melatonin in people with Neonatal Diseases and Abnormalities and Neonatal Mortality, run by Ain Shams University at 1 site in Egypt.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 28 days
- Conditions the study is for
- Neonatal Diseases and Abnormalities, Neonatal Mortality, Pulmonary Arterial Hypertension
- What is being tested?
- Melatonin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteEgypt
- Study dates
- 15 May 2024to 15 Mar 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 28 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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).
Who cannot join
- Neonates with major congenital anomalies like congenital heart diseases
- NPO or any contraindications to oral intake
- Neonates with suspected inborn error of metabolism
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Melatonin as an Adjunct Therapy to Milrinone for Pulmonary Hypertension in Full Term Neonates
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.
Read the 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.
- Conditions
- Neonatal Diseases and Abnormalities, Neonatal Mortality, Pulmonary Arterial Hypertension, Pulmonary Arterial Hypertension, Children
- Being tested
- Melatonin, Placebo
- Keywords
- Neonate, Pulmonary hypertension, Melatonin, Milrinon
- Medical subject headings
- Congenital, Hereditary, and Neonatal Diseases and Abnormalities, Pulmonary Arterial Hypertension, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelatoninDrug
oral melatonin 3 mg/kg/day divided in 3 doses , after enteral feeding, for 3 consecutive days, as combined therapy to milrinone
PlaceboOther
Equivalent amount of distilled water will be given every hours as combined therapy to milrinone
| Study group | Role | What they receive |
|---|---|---|
| Intervention group melatonin group | Experimental | 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). Receives: Drug: Melatonin |
| Control group | Placebo comparator | 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 Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pulmonary arterial pressure
Measuring pulmonary artery pressure by echocardiography
Measured: After 72 hours of the start of the drug
FiO2
FiO2 needs to maintain oxygen saturation monitored non invasively
Measured: Hourly for 3 days
Secondary outcomes (1)
Hospital stay
Duration of hospital stay
Measured: One month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2024
- Study start15 May 2024
- Primary completion15 Dec 2024
- Study completion15 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Neonatal Diseases and AbnormalitiesStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mariam Ibrahim, Ain Shams University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06685679
- Sponsor's protocol ID
- Melatonin in pulmonary hyperte
- Status last verified
- Nov 2024
- First submitted
- 11 Nov 2024
- Last updated
- 10 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Information can be shared upon accepted request
Publications
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.
PubMed 356244521- 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
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Melatonin as an Adjunct Therapy to Milrinone for Pulmonary Hypertension in Full Term Neonates
- ClinicalTrials.gov ID
- NCT06685679
- Acronym / sponsor ID
- Melatonin in pulmonary hyperte
- Conditions
- Neonatal Diseases and Abnormalities, Neonatal Mortality, Pulmonary Arterial Hypertension, Pulmonary Arterial Hypertension, Children
- Keywords
- Neonate, Pulmonary hypertension, Melatonin, Milrinon
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- 15 May 2024 (actual)
- Primary completion
- 15 Dec 2024 (actual)
- Study completion
- 15 Mar 2025 (actual)
- First posted
- 12 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention group melatonin group | Experimental | Drug: MelatoninIntervention 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 comparator | Other: PlaceboControl 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 |
Who may qualify
- Ages
- Up to 28 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- 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).
Key exclusion criteria (3 listed)
- Neonates with major congenital anomalies like congenital heart diseases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Melatoninoral melatonin 3 mg/kg/day divided in 3 doses , after enteral feeding, for 3 consecutive days, as combined therapy to milrinone | Drug | Intervention group melatonin group |
| PlaceboEquivalent amount of distilled water will be given every hours as combined therapy to milrinone | Other | Control group |
Primary outcome
Pulmonary arterial pressure
Time frame: After 72 hours of the start of the drug
Measuring pulmonary artery pressure by echocardiography
FiO2
Time frame: Hourly for 3 days
FiO2 needs to maintain oxygen saturation monitored non invasively
1 secondary outcome
Hospital stay
Time frame: One month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2025.
- Background: PubMed 35624452Chetan 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.
- Background1- 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
- Individual participant dataSharing planned: Yes. Information can be shared upon accepted request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Melatonin in people with Neonatal Diseases and Abnormalities and Neonatal Mortality, run by Ain Shams University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pulmonary arterial pressure (time frame: After 72 hours of the start of the drug). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06685679, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2025.