| CTRI Number |
CTRI/2025/02/081400 [Registered on: 27/02/2025] Trial Registered Prospectively |
| Last Modified On: |
13/02/2026 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
Inhaled Milrinone for PPHN in neonates |
|
Scientific Title of Study
|
Inhaled Milrinone as adjuvant to oral
Sildenafil in persistent pulmonary hypertension of newborn: a parallel group
randomized pilot trial |
| Trial Acronym |
iMil |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Rameshwar Prasad |
| Designation |
Associate Professor, Neonatology |
| Affiliation |
All India Institute of Medical Sciences, Patna |
| Address |
Department of Neonatology, BGA B block, IPD building, All India Institute of Medical Sciences, Patna
Patna
BIHAR
801507
India |
| Phone |
8210133306 |
| Fax |
|
| Email |
dr.rameshwar11334@aiimspatna.org |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Rameshwar Prasad |
| Designation |
Associate Professor, Neonatology |
| Affiliation |
All India Institute of Medical Sciences, Patna |
| Address |
Department of Neonatology, BGA B block, IPD building, All India Institute of Medical Sciences, Patna
BIHAR
801507
India |
| Phone |
8210133306 |
| Fax |
|
| Email |
dr.rameshwar11334@aiimspatna.org |
|
Details of Contact Person
Public Query
|
| Name |
Dr Rameshwar Prasad |
| Designation |
Associate Professor, Neonatology |
| Affiliation |
All India Institute of Medical Sciences, Patna |
| Address |
Department of Neonatology, BGA B block, IPD building, All India Institute of Medical Sciences, Patna
BIHAR
801507
India |
| Phone |
8210133306 |
| Fax |
|
| Email |
dr.rameshwar11334@aiimspatna.org |
|
|
Source of Monetary or Material Support
|
| All India Insititute of Medical Sciences, Patna, PIN-801507, Bihar |
| Indian Council of Medical Research, V. Ramalingaswami Bhawan, P.O. Box No. 4911
Ansari Nagar, New Delhi - 110029, India. |
|
|
Primary Sponsor
|
| Name |
Dr Rameshwar Prasad |
| Address |
Department of Neonatology, BGA B Block, IPD building, All India Institute of Medical Sciences, Patna |
| Type of Sponsor |
Other [Self] |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Rameshwar Prasad |
All India institute of Medical Sciences |
Department of Neonatology, BGA B block, IPD building, ground floor, All India Institute of Medical Sciences, PAtna
Patna
BIHAR |
8210133306
dr.rameshwar11334@aiimspatna.org |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 2 |
| Name of Committee |
Approval Status |
| Institute ethics committee AIIMS Patna |
Approved |
| Institute Ethics Committee-AIIMS-Patn a |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: P293||Persistent fetal circulation, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Inhaled Milrinone, Oral Sildenafil |
Inhaled milrinone (inj milrinone 1mg/ml, dissolved in 10 ml NS)
The dose of inhaled milrinone will be 50 microgram/kg bodyweight over 10
minutes
Frequency- every 8 hourly.
Route of administration- Milrinone will be administered through an ultrasonic mesh nebulizer attached to the inspiratory branch of the respiratory limb of the ventilator near the endotracheal tube.
Total duration of intervention- 48 hrs (After completion of the 48-hour study, patients could transition to continuous IV milrinone or IV Sildenafil at the discretion of the treating neonatologist)
Sildenafil tablet @ 1 to 2 mg/kg/dose 6 hourly. A 20 mg sildenafil citrate tablet will be dissolved in 20 milliliters of distilled water, and then the prescribed dosage will be administered via an orogastric tube.
Concomitant medications will be used according to unit protocol. |
| Comparator Agent |
Oral Sildenafil |
Sildenafil Tablet @ 1 to 2 mg/kg/dose 6 hourly for 48 hrs. A 20 mg sildenafil citrate tablet will be dissolved in 20 milliliters of distilled water, and then the prescribed dosage will be administered via an orogastric tube. Total duration of intervention-48 hrs.
(After completion of the 48-hour study, patients could transition to continuous IV milrinone or IV Sildenafil at the discretion of the treating neonatologist)
Concomitant medications will be used according to unit protocol. |
|
|
Inclusion Criteria
|
| Age From |
0.00 Month(s) |
| Age To |
1.00 Month(s) |
| Gender |
Both |
| Details |
All neonates admitted to level III NICU will be screened for eligibility 1.Gestation equal to or more than 34 0/7 week post menstrual age by best obstetric estimate and a birth weight equal to or more than 2000
g
2.Age less than 28 days
3.On mechanical ventilation
4.Clinical diagnosis of PPHN
5.Entry criteria: Hypoxemic respiratory failure i.e. Oxygenation index (OI) equal to or more than 10 and less than 40 (OI equals mean airway pressure x FiO2) divided by PaO2 x (100).
6.Screening echocardiogram to assess the presence of PPHN (defined as evidence of right to left or bidirectional
shunting) and to eliminate subjects with large left to right intracardiac or ductal shunting or significant congenital heart disease. |
|
| ExclusionCriteria |
| Details |
1.Lethal congenital anomalies or obvious syndrome 2. Presence of congenital heart disease, congenital diaphragmatic hernia, lung hypoplasia syndromes), except: patent ductus arteriosus, patent foramen ovale, small atrial septal defect, or small ventricular septal defect 3. Bleeding diathesis (abnormal coagulation screen/platelet 10,0000/ mm3) 4. The presence of grade III or more grade of Intraventricular haemorrhage: Screening cranial ultrasound before randomization 5. Severe hypotension (mean blood pressure 35 mm Hg) or shock (heart rate 180 beats per minute, capillary refill time 3 second, urine output 0.5ml/kg/hour) unresponsive to medical management (≥ 2 inotropes). 6. Hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia 7. Evidence of renal impairment (Creatinine 1.5 mg/dl). 8. In the opinion of investigator, inappropriate for study for any reason. |
|
|
Method of Generating Random Sequence
|
Permuted block randomization, variable |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Outcome Assessor Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| change in oxygenation index |
at 48 hrs |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| All-cause mortality |
28 days of life |
| Systolic pulmonary artery pressure |
48hrs |
| Length of hospital stay |
till discharge |
| Duration of mechanical ventilation |
28 days |
| Mean blood pressure |
24hr |
| Treatment failure |
48 hrs |
| Change in OI |
24 hrs |
| Time to decrease in OI |
48 hrs |
Adverse events-
1. Hypotension: -Hypotension requiring 2 or more inotropes for normalization of BP
2. Pulmonary hemorrhage
4. Any other adverse event |
48 hrs |
| Safety laboratory tests- complete blood count, AST, ALT, serum creatinine |
48 hrs |
|
|
Target Sample Size
|
Total Sample Size="30"
Sample Size from India="30"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 2/ Phase 3 |
|
Date of First Enrollment (India)
|
15/03/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Persistent pulmonary hypertension of newborn (PPHN) is characterized by high pulmonary vascular resistance, increased pulmonary pressure and severe hypoxia in newborns. Inhaled nitric oxide (iNO), the mainstay of treatment of PPHN, is costly, not readily available and needs special equipment and expertise. Moreover, up to 40% of newborns receiving iNO show partial or no response. In settings where iNO is unavailable, phosphodiesterase (PDE) inhibitors, sildenafil (PDE V inhibitor) and milrinone (PDE III inhibitor), are commonly used for treating PPHN. Novelty Increasing the levels of both cAMP (PDE III inhibitor) and cGMP (PDE V inhibitor) together may have a synergistic effect. Due to systemic side effects of Intravenous milrinone, inhalational route may have several advantages.
Inhalational milrinone has been studied in adults and children. So far only one study has used inhalational milrinone in neonates with PPHN. Synergistic effect of inhalational milrinone as an adjuvant to oral Sildenafil has not been studied in newborn. We hypothesize that inhaled milrinone used in conjunction with oral Sildenafil will be superior to oral Sildenafil alone in improving oxygenation without an increase in sideeffects in neonates ≥34 weeks gestation and ≥ 2000 g with a clinical or echocardiography diagnosis of PPHN.
|