Treatment Investigational New Drug Experience With Survanta (Beractant)

PEDIATRICS ◽  
1993 ◽  
Vol 91 (3) ◽  
pp. 546-551
Author(s):  
Elizabeth M. Zola ◽  
A. M. Overbach ◽  
J. Harry Gunkel ◽  
Brian R. Mitchell ◽  
Barbara T. Nagle ◽  
...  
Keyword(s):  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Neonatal Intensive Care ◽  
Distress Syndrome ◽  
Ductus Arteriosus ◽  
Pulmonary Hemorrhage ◽  
The United States ◽  
Controlled Trials ◽  
Randomized Controlled Clinical Trials ◽  
New Drug

From September 1989 through July 1991, before commercial availability, Survanta (beractant intratracheal suspension), a modified bovine-derived surfactant used for prevention and treatment of neonatal respiratory distress syndrome, was made available to 231 neonatal intensive care units in the United States and Canada under a Treatment Investigational New Drug protocol. Results of this open clinical experience are reported. Investigators could give one dose of Survanta soon after birth to neonates weighing 600 to 1250 g (prevention strategy). Neonates weighing 600 to 1750 g who were not treated at birth could begin Survanta therapy if respiratory distress syndrome developed within 8 hours of birth (rescue strategy). All neonates could receive up to three more doses over the first 48 hours of life at minimum intervals of 6 hours if they met retreatment criteria. Qualifications for enrollment closely matched those used in previous randomized controlled clinical trials. This report includes results from 8168 neonates who completed the study. Treatment Investigational New Drug rates for intracranial hemorrhage, patent ductus arteriosus, pulmonary hemorrhage, pulmonary air leaks, bronchopulmonary dysplasia, death or bronchopulmonary dysplasla, pulmonary interstitial emphysema, pretreatment sepsis, and posttreatment sepsis were less than for treated neonates in the controlled trials and survival was equivalent across studies. Problems with treatment administration were reported with 30.4% of doses, while adverse events were reported in 0.5% of neonates. The results of the Treatment Investigational New Drug protocol revealed no new safety concerns associated with the widespread use of Survanta and confirmed the safety profile established in earlier controlled trials.

scholarly journals Treatment with senicapoc in a porcine model of acute respiratory distress syndrome

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Asbjørn G. Petersen ◽  
Peter C. Lind ◽  
Anne-Sophie B. Jensen ◽  
Mark A. Eggertsen ◽  
Asger Granfeldt ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Bronchoalveolar Lavage ◽  
Primary Endpoint ◽  
Bronchoalveolar Lavage Fluid ◽  
Distress Syndrome ◽  
Pulmonary Hemorrhage ◽  
Lavage Fluid

Abstract Background Senicapoc is a potent and selective blocker of KCa3.1, a calcium-activated potassium channel of intermediate conductance. In the present study, we investigated whether there is a beneficial effect of senicapoc in a large animal model of acute respiratory distress syndrome (ARDS). The primary end point was the PaO2/FiO2 ratio. Methods ARDS was induced in female pigs (42–49 kg) by repeated lung lavages followed by injurious mechanical ventilation. Animals were then randomly assigned to vehicle (n = 9) or intravenous senicapoc (10 mg, n = 9) and received lung-protective ventilation for 6 h. Results Final senicapoc plasma concentrations were 67 ± 18 nM (n = 9). Senicapoc failed to change the primary endpoint PaO2/FiO2 ratio (senicapoc, 133 ± 23 mmHg; vehicle, 149 ± 68 mmHg). Lung compliance remained similar in the two groups. Senicapoc reduced the level of white blood cells and neutrophils, while the proinflammatory cytokines TNFα, IL-1β, and IL-6 in the bronchoalveolar lavage fluid were unaltered 6 h after induction of the lung injury. Senicapoc-treatment reduced the level of neutrophils in the alveolar space but with no difference between groups in the cumulative lung injury score. Histological analysis of pulmonary hemorrhage indicated a positive effect of senicapoc on alveolar–capillary barrier function, but this was not supported by measurements of albumin content and total protein in the bronchoalveolar lavage fluid. Conclusions In summary, senicapoc failed to improve the primary endpoint PaO2/FiO2 ratio, but reduced pulmonary hemorrhage and the influx of neutrophils into the lung. These findings open the perspective that blocking KCa3.1 channels is a potential treatment to reduce alveolar neutrophil accumulation and improve long-term outcome in ARDS.

Double-Blind, Randomized Trial of a Calf Lung Surfactant Extract Administered at Birth to Very Premature Infants for Prevention of Respiratory Distress Syndrome

PEDIATRICS ◽  
1985 ◽  
Vol 76 (4) ◽  
pp. 593-599 ◽  
Author(s):  
Donald L. Shapiro ◽  
Robert H. Notter ◽  
Frederick C. Morin ◽  
Karl S. Deluga ◽  
Leonard M. Golub ◽  
...  
Keyword(s):  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Premature Infants ◽  
Neonatal Intensive Care ◽  
Distress Syndrome ◽  
Lung Surfactant ◽  
Treated Group ◽  
Control Group ◽  
Double Blind ◽  
Severe Respiratory Distress

Organic solvent extraction of surfactant obtained by lavage of calf lungs yields a highly surfaceactive material. A double blind, randomized clinical trial to determine the effect of this material on respiratory distress syndrome in premature infants was initiated in the Neonatal Intensive Care Unit at the University of Rochester in December 1983. Infants 25 to 29 weeks gestational age were eligible for entry into the trial. At the time of this interim analysis 32 patients had been randomly selected and entered into the trial, 16 surfactant-treated patients and 16 in a control group who received only saline. At birth, intrapulmonary instillation of the calf lung surfactant extract dispersed in saline or saline alone occurred in the delivery room immediately after intubation and prior to ventilation; infants were then ventilated and treated as usual. At 6, 12, 24, 48, and 72 hours after birth, the severity of respiratory distress was categorized as either minimal, intermediate, or severe based on oxygen and mean airway pressure requirements. Differences observed at six hours after birth were of marginal significance, but at 12 and 24 hours the surfactant-treated group had significantly (P < .01) less severe respiratory distress compared with the control group. Differences between treated and control infants were not statistically significant at 48 and 72 hours after birth. In four surfactant-treated infants the severity of respiratory distress worsened between 24 and 48 hours after birth, suggesting that one dose of surfactant at birth may not be sufficient for some infants.

scholarly journals Surfactant Replacement Therapy for Respiratory Distress Syndrome in the Newborn: A Review

2017 ◽  
Vol 40 (1) ◽  
pp. 26-30
Author(s):  
Tahsinul Amin ◽  
Mohammod Shahidullah
Keyword(s):  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Pulmonary Hemorrhage ◽  
Surfactant Therapy ◽  
Respiratory Morbidity ◽  
Exogenous Surfactant ◽  
Surfactant Replacement ◽  
Surfactant Deficiency ◽  
Surfactant Replacement Therapy

Respiratory failure secondary to surfactant deficiency is a major cause of morbidity and mortality in low birth weight premature infants. Surfactant therapy substantially reduces mortality and respiratory morbidity for this population. Exogenous surfactant therapy has become well established in newborn infants with respiratory distress. Many aspects of its use have been well evaluated in high-quality trials and systematic reviews. Secondary surfactant deficiency also contributes to acute respiratory morbidity in late-preterm and term neonates with meconium aspiration syndrome, pneumonia/ sepsis, and perhaps pulmonary hemorrhage; surfactant replacement may be beneficial for these infants. This article summarizes the evidence and gives recommendations for the use of surfactant therapy for respiratory distress syndrome (RDS) in newborn.Bangladesh J Child Health 2016; VOL 40 (1) :26-30

scholarly journals The Role of Extra Corporeal Membrane Oxygenation for Treatment of the Adult Respiratory Distress Syndrome: Review and Quantitative Analysis

2008 ◽  
Vol 36 (2) ◽  
pp. 152-161 ◽  
Author(s):  
R. P. Chalwin ◽  
J. L. Moran ◽  
P. L. Graham
Keyword(s):  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Adult Respiratory Distress Syndrome ◽  
Randomised Controlled Trials ◽  
Distress Syndrome ◽  
Controlled Trials ◽  
Extra Corporeal Membrane Oxygenation ◽  
Membrane Oxygenation ◽  
Randomised Controlled

The role of Extra corporeal membrane oxygenation (ECMO) has not been formally validated for patients with adult respiratory distress syndrome. In anticipation of publication of the conventional ventilation versus ECMO in severe adult respiratory failure (CESAR) trial, the role of ECMO in this setting was reviewed. An electronic search for studies reporting the use of ECMO for the treatment of adult respiratory distress syndrome revealed two randomised controlled trials and three non-controlled trials. Bayesian analysis on the two randomised controlled trials produced an odds ratio mortality of 1.28 (credible interval 0.24 to 6.55) demonstrating no significant harm or benefit. Pooling was not possible for the non-controlled studies because of differing admission status and ECMO selection criteria and an inability to control for these differences in the absence of individual patient data. A large number (n=35) of case series have been published with generally more positive results. We also present a comprehensive narrative commentary on the history, current practice and future for ECMO. ECMO, as rescue therapy for adult respiratory distress syndrome, appears to be an unvalidated rescue treatment option. Analysis and review of trial data does not support its application; however the body of reported cases suggests otherwise. Until the CESAR trial provides an authoritative answer ECMO will continue to be offered on a case by case basis.

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