Endovenous Sildenafil Early Management in Newborns Pulmonary Hypertension

NCT04912726 | Withdrawn DMC

• 1 other identifier: 234
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Sildenafil is currently approved for the management of pulmonary hypertension of the newborn, with the availability of intravenous presentation it has been seen that the severity condition has already established, many times these patients do not have the adequate clinical response and there are no studies to date that evaluate the efficacy and safety of the same when it is started early in these patients, therefore we plan a randomized clinical trial to determine the efficacy and safety of the administration of intravenous sildenafil for early management of newborns with persistent pulmonary hypertension of the newborn.

Conditions

Hypertension, Pulmonary

Keywords

newborn; intravenous sildenafil; Hypertension, Pulmonary

Outcome Measures

Primary Outcomes (1)

• 20% decrease in estimated pulmonary artery pressure

  Evaluate the efficacy in lowering the estimated pulmonary artery pressure by 20% and improved survival with early use of intravenous sildenafil at a loading dose of 0.4 mg / kg in 3 hours, followed by continuous infusion at 1.6 mg / kg / day versus conventional treatment plus placebo in neonates with persistent pulmonary hypertension of the newborn.

  7 days

Secondary Outcomes (3)

• Duration of mechanical ventilation

  7 days

• Duration of inotropic therapy

  7 days

• Adverse events

  7 days

Study Arms (2)

Intervention

EXPERIMENTAL

The intervention group will receive intravenous sildenafil loading dose of 0.4 mg / kg in 3 hours and continue in continuous infusion at 1.6 mg / kg / day (0.067 mg / kg / h).

Drug: Sildenafil Injectable Product

Placebo

NO INTERVENTION

The control group will receive placebo at the same loading dose and infusion with 0.9% saline solution plus standard management under the unit protocol immediately after the echocardiographic diagnosis.

Interventions

Sildenafil Injectable Product DRUG

The intervention group will receive intravenous sildenafil loading dose of 0.4 mg / kg in 3 hours and continue in continuous infusion at 1.6 mg / kg / day (0.067 mg / kg / h).

Also known as: Intravenous sildenafil

Intervention

Eligibility Criteria

• Age: Up to 10 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Newborns with gestational age ≥ 34 weeks and less than 10 days old, from the delivery room, joint accommodation, surgery at the Niño Jesus Hospital and referred from other institutions with an echocardiographic diagnosis of persistent pulmonary hypertension of the newborn. A diagnosis of persistent pulmonary hypertension of the newborn will be made if any of the following criteria are identified in the absence of cyanotic congenital heart disease by echocardiography: Tricuspid regurgitant jet with a pressure gradient ≥ 2/3 of systemic systolic blood pressure; intraventricular septum that flattens or slopes into the left ventricular cavity; bidirectional or right-to-left flow through patent ductus arteriosus; pulmonary artery acceleration time \<40 milliseconds

You may not qualify if:

• Congenital heart disease or fatal congenital anomalies
• Oxygenation Index (IO) \> 15
• No parental consent

Sponsors & Collaborators

• Universidad del Norte: lead

Related Publications (8)

• Martinho S, Adao R, Leite-Moreira AF, Bras-Silva C. Persistent Pulmonary Hypertension of the Newborn: Pathophysiological Mechanisms and Novel Therapeutic Approaches. Front Pediatr. 2020 Jul 24;8:342. doi: 10.3389/fped.2020.00342. eCollection 2020.

  PMID: 32850518 BACKGROUND

• Jain A, McNamara PJ. Persistent pulmonary hypertension of the newborn: Advances in diagnosis and treatment. Semin Fetal Neonatal Med. 2015 Aug;20(4):262-71. doi: 10.1016/j.siny.2015.03.001. Epub 2015 Apr 2.

  PMID: 25843770 BACKGROUND

• Fuloria M, Aschner JL. Persistent pulmonary hypertension of the newborn. Semin Fetal Neonatal Med. 2017 Aug;22(4):220-226. doi: 10.1016/j.siny.2017.03.004. Epub 2017 Mar 23.

  PMID: 28342684 BACKGROUND

• Baquero H, Soliz A, Neira F, Venegas ME, Sola A. Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study. Pediatrics. 2006 Apr;117(4):1077-83. doi: 10.1542/peds.2005-0523.

  PMID: 16585301 BACKGROUND

• Pedersen J, Hedegaard ER, Simonsen U, Kruger M, Infanger M, Grimm D. Current and Future Treatments for Persistent Pulmonary Hypertension in the Newborn. Basic Clin Pharmacol Toxicol. 2018 Oct;123(4):392-406. doi: 10.1111/bcpt.13051. Epub 2018 Jul 19.

  PMID: 29855164 BACKGROUND

• Lakshminrusimha S, Mathew B, Leach CL. Pharmacologic strategies in neonatal pulmonary hypertension other than nitric oxide. Semin Perinatol. 2016 Apr;40(3):160-73. doi: 10.1053/j.semperi.2015.12.004. Epub 2016 Jan 14.

  PMID: 26778236 BACKGROUND

• El-Khuffash A, McNamara PJ, Breatnach C, Bussmann N, Smith A, Feeney O, Tully E, Griffin J, de Boode WP, Cleary B, Franklin O, Dempsey E. The use of milrinone in neonates with persistent pulmonary hypertension of the newborn - a randomised controlled trial pilot study (MINT 1): study protocol and review of literature. Matern Health Neonatol Perinatol. 2018 Dec 3;4:24. doi: 10.1186/s40748-018-0093-1. eCollection 2018.

  PMID: 30524749 BACKGROUND

• Uslu S, Kumtepe S, Bulbul A, Comert S, Bolat F, Nuhoglu A. A comparison of magnesium sulphate and sildenafil in the treatment of the newborns with persistent pulmonary hypertension: a randomized controlled trial. J Trop Pediatr. 2011 Aug;57(4):245-50. doi: 10.1093/tropej/fmq091. Epub 2010 Oct 4.

  PMID: 20923790 BACKGROUND

MeSH Terms

Conditions

Hypertension, Pulmonary

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Assignment concealment will be ensured using sealed and sequenced opaque (dark) sealed envelopes containing the assignments. An investigator will carry out the assignment, write down the assignment number in a specific format, seal the opaque envelope and number it consecutively. These envelopes will be stored in the neonatal intensive care unit of the hospital child jesus where the study will be carried out. Once a subject has met the inclusion criteria, the neonatal intensive care unit pharmacy service will be notified, staff not participating in the study who will make a phone call to the investigator so that he can assign the label number to the new subject who I enter the study, the pharmacy shift personnel are in charge of labeling and delivering the product to the nursing staff. The active product intravenous sildenafil and the placebo are packaged in identical burette, the burette content is visible and the coloration is transparent.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, controlled, double-blind clinical trial

Study Record Dates

• First Submitted: May 24, 2021
• First Posted: June 3, 2021
• Study Start: January 1, 2025
• Primary Completion (Estimated): June 15, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: December 6, 2024

Record last verified: 2024-12