Safety and tolerability of subcutaneous treprostinil in newborns with congenital diaphragmatic hernia and life-threatening pulmonary hypertension

Carpentier, E; Mur, Sébastien; Aubry, E.; Pognon, L.; Rakza, Thameur; Flamein, Florence; Sharma, Dyuti; Tourneux, P.; Storme, Laurent

doi:10.1016/j.jpedsurg.2017.03.058

Cited by 32 publications

(25 citation statements)

References 16 publications

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“…Such beneficial effect of subcutaneous treprostinil is also observed in a select group of patients with chronic lung disease and severe PAH (former premature infants, patients with congenital diaphragmatic hernia) who have not responded adequately to conservative therapies …”

Section: Discussionmentioning

confidence: 93%

Use of subcutaneous treprostinil in pediatric pulmonary arterial hypertension—Bridge‐to‐transplant or long‐term treatment?

Ablonczy

Tordas

Kis

et al. 2017

Pediatric Transplantation

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PAH is a progressive life-threatening disease in children. While parenteral prostacyclin therapy improves survival in patients with severe PAH, central line-related complications are common. Our aim was to assess the efficacy, safety, and tolerability of subcutaneous treprostinil treatment in pediatric PAH patients. Eight patients were treated with subcutaneous treprostinil at the Pediatric Heart Center Budapest. Indications for subcutaneous treprostinil therapy were clinical worsening and/or echocardiographic progression or switch from intravenous to subcutaneous therapy. Following treprostinil initiation, clinical status improved or did not change in four of eight patients. Two patients were lost early during treprostinil therapy, parenteral treprostinil as a rescue therapy being insufficient in these cases. The final dose in long-term treated patients was between 60 and 100 ng/kg/min. Aside from thrombocytopenia, other severe side effects were not observed. Potts shunt was performed as palliative treatment in two cases. Three patients had successful lung transplantation, and one died while on the waiting list. Long-term subcutaneous treprostinil could be a safe and well-tolerated therapy in children with severe PAH even at higher doses. It may serve as an alternative to intravenous prostacyclin treatment allowing to avoid the potential complications of permanent central line placement.

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Section: Discussionmentioning

confidence: 93%

Use of subcutaneous treprostinil in pediatric pulmonary arterial hypertension—Bridge‐to‐transplant or long‐term treatment?

Ablonczy

Tordas

Kis

et al. 2017

Pediatric Transplantation

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“…The potential vasodilatory activity and reversal of remodeling that occurs in the pulmonary vascular wall provide the rationale for prostacyclin therapy for treating PHT in both etiologies. 11 In this study, we used OI to determinate the severity of PHT as a way of measuring the acute effect of treprostinil. OI is an accurate indicator of disease severity at the time of measurement.…”

Section: Discussionmentioning

confidence: 99%

Neonates Effects and Tolerability of Treprostinil in Hypertension with Persistent Pulmonary

et al. 2019

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Objective The aim of this study was to establish the effects of treprostinil in congenital diaphragmatic hernia (CDH) patients with persistent pulmonary hypertension (PHT) after 1 week of treatment. Drug effects were assessed by oxygenation index (OI), clinical end points, serial biochemical markers, and pre- and posttreatment echocardiogram. Treatment complications were also described. Study Design This is a quasi-experimental study of neonates with PHT admitted to the NICU within 48 hours showing persistent clinical instability, receiving mechanical ventilation with FiO2 > 60%, milrinone therapy, and inhaled nitric oxide. Clinical data were compared before and after treprostinil treatment. Results Seventeen neonates met the inclusion criteria. Median age was 17 days. Before treatment, median OI was 20 (IQR: 12–27). Suprasystemic PHT was estimated by echocardiogram in 8/17 patients; the rest were systemic. After 1 week of treatment, 15/17 patients were alive and median OI was 8 (IQR: 5–12, p = 0.0089). There were no statistically significant changes in laboratory data. Echocardiogram still showed suprasystemic PHT in 20% of patients. Adverse effects included hypotension, hematoma at the infusion site, and surgical persistent ductus arteriosus (PDA) closure in 4/17 patients. Fourteen patients were discharged. The median treatment time was 61 days. Conclusion Treprostinil was well tolerated with satisfactory clinical response. Further studies are required to identify early responder subgroups.

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“…Treprostinil, a synthetic prostacyclin analog, is a potent pulmonary vasodilator approved for the treatment of idiopathic pulmonary arterial hypertension in adults and children. 4,5 We and others have reported good tolerance and clinical improvement with treprostinil as off-label, add-on therapy in neonates with PPHN refractory to inhaled nitric oxide (iNO) and sildenafil, [6][7][8][9][10] whereas clinical efficacy is currently investigated in an ongoing placebo-controlled randomized trial as add-on intervention to iNO (NCT02261883). In neonates with severe PPHN enduring persistent hypoxemia and hemodynamic instability despite aggressive medical management, therapy with extracorporeal membrane oxygenation (ECMO) is indicated.…”

Section: B R I E F R E P O R Tmentioning

confidence: 99%

Treprostinil Attains Clinically Therapeutic Concentrations in Neonates with Pulmonary Hypertension on Extracorporeal Membrane Oxygenation Support

et al. 2020

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Background: Treprostinil is a prostacyclin analog used for treatment of pulmonary hypertension (PH) in adults and children, currently awaiting clinical assessment for use in neonates.Objectives: We aimed to investigate the use of treprostinil in neonates with PH on extracorporeal membrane oxygenation (ECMO) support and measure plasma concentrations of the drug.Methods: This is a retrospective case‐series with prospectively collected blood samples, conducted in a quaternary care neonatal intensive care unit. Brain natriuretic peptide, cardiac function on Doppler echocardiography, and the occurrence of adverse effects was monitored. Plasma concentrations were measured using high‐performance liquid chromatography and mass spectrometry.Results: Four patients with PH requiring ECMO therapy were studied. Treprostinil doses of 20–58 ng/kg/min reached concentrations of 0.99–4.39 ng/ml and induced clinical improvement. Infusion of treprostinil was associated with improved right ventricular function, reversed right‐to‐left shunting through the ductus arteriosus, and stable or decreasing need for vasopressor support. No adverse effects were observed.Conclusions: This is the first study to report clinically therapeutic treprostinil concentrations in circulating plasma after treprostinil administration in neonates on ECMO, with associated clinical improvement of PH and no signs of hemodynamic instability.

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Safety and tolerability of subcutaneous treprostinil in newborns with congenital diaphragmatic hernia and life-threatening pulmonary hypertension

Cited by 32 publications

References 16 publications

Use of subcutaneous treprostinil in pediatric pulmonary arterial hypertension—Bridge‐to‐transplant or long‐term treatment?

Use of subcutaneous treprostinil in pediatric pulmonary arterial hypertension—Bridge‐to‐transplant or long‐term treatment?

Neonates Effects and Tolerability of Treprostinil in Hypertension with Persistent Pulmonary

Treprostinil Attains Clinically Therapeutic Concentrations in Neonates with Pulmonary Hypertension on Extracorporeal Membrane Oxygenation Support

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