Goat lung surfactant for treatment of respiratory distress syndrome among preterm neonates: a multi-site randomized non-inferiority trial

Kajal Jain, Sushma Nangia, Vishnu Bhat Ballambattu, Venkataseshan Sundaram, M Jeeva Sankar, Siddharth Ramji, Sreenivas Vishnubhatla, Anu Thukral, Yogendra Kumar Gupta, Nishad Plakkal, Mangalabharathi Sundaram, Mamta Jajoo, Praveen Kumar, Kumutha Jayaraman, Ashish Jain, Arvind Saili, Anitha Murugesan, Deepak Chawla, Srinivas Murki, Ruchi Nanavati, Suman Rao, Umesh Vaidya, Ashish Mehta, Kamal Arora, Jayashree Mondkar, Sugandha Arya, Monika Bahl, Alpana Utture, Swati Manerkar, Swarna Rekha Bhat, Tushar Parikh, Manish Kumar, Anurag Bajpai, Sindhu Sivanandan, Pawandeep Kaur Dhawan, Gayatri Vishwakarma, Sudhakar Bangera, Sumit Kumar, Shridhar Gopalakrishnan, Atul Jindal, Chandra Kumar Natarajan, Anumeet Saini, Sukanya Karunanidhi, Meenakshi Malik, Parul Narang, Gurkirat Kaur, Chander Prakash Yadav, Ashok Deorari, Vinod K Paul, Ramesh Agarwal, Kajal Jain, Sushma Nangia, Vishnu Bhat Ballambattu, Venkataseshan Sundaram, M Jeeva Sankar, Siddharth Ramji, Sreenivas Vishnubhatla, Anu Thukral, Yogendra Kumar Gupta, Nishad Plakkal, Mangalabharathi Sundaram, Mamta Jajoo, Praveen Kumar, Kumutha Jayaraman, Ashish Jain, Arvind Saili, Anitha Murugesan, Deepak Chawla, Srinivas Murki, Ruchi Nanavati, Suman Rao, Umesh Vaidya, Ashish Mehta, Kamal Arora, Jayashree Mondkar, Sugandha Arya, Monika Bahl, Alpana Utture, Swati Manerkar, Swarna Rekha Bhat, Tushar Parikh, Manish Kumar, Anurag Bajpai, Sindhu Sivanandan, Pawandeep Kaur Dhawan, Gayatri Vishwakarma, Sudhakar Bangera, Sumit Kumar, Shridhar Gopalakrishnan, Atul Jindal, Chandra Kumar Natarajan, Anumeet Saini, Sukanya Karunanidhi, Meenakshi Malik, Parul Narang, Gurkirat Kaur, Chander Prakash Yadav, Ashok Deorari, Vinod K Paul, Ramesh Agarwal

Abstract

Objective: To investigate the safety and efficacy of goat lung surfactant extract (GLSE) compared with bovine surfactant extract (beractant; Survanta®, AbbVie, USA) for the treatment of neonatal respiratory distress syndrome (RDS).

Study design: We conducted a double-blind, non-inferiority, randomized trial in seven Indian centers between June 22, 2016 and January 11, 2018. Preterm neonates of 26 to 32 weeks gestation with clinical diagnosis of RDS were randomized to receive either GLSE or beractant. Repeat dose, if required, was open-label beractant in both the groups. The primary outcome was a composite of death or bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age (PMA). Interim analyses were done by an independent data and safety monitoring board (DSMB).

Result: After the first interim analyses on 5% enrolment, the "need for repeat dose(s) of surfactant" was added as an additional primary outcome and enrolment restricted to intramural births at five of the seven participating centers. Following second interim analysis after 98 (10% of 900 planned) neonates were enroled, DSMB recommended closure of study in view of inferior efficacy of GLSE in comparison to beractant. There was no significant difference in the primary outcome of death or BPD between GLSE group (n = 52) and beractant group (n = 46) (50.0 vs. 39.1%; OR 1.5; 95% CI 0.7-3.5; p = 0.28). The need for repeat dose of surfactant was significantly higher in GLSE group (65.4 vs. 17.4%; OR 9.0; 95% CI 3.5-23.3; p < 0.001).

Conclusions: Goat lung surfactant was less efficacious than beractant (Survanta®) for treatment of RDS in preterm infants. Reasons to ascertain inferior efficacy of goat lung surfactant requires investigation and possible mitigating strategies in order to develop a low-cost and effective surfactant.

Trial registration: ClinicalTrials.gov NCT02774044.

Conflict of interest statement

The authors declare that they have no conflict of interest. Cadila Pharmaceutical Ltd, Ahmedabad, India provided goat lung surfactant free of cost. It had, however, no role in protocol development, implementation of the trial, or interpretation and publication of trial results.

Figures

Fig. 1
Fig. 1
Participant flow
Fig. 2
Fig. 2
Mean FiO2 values from 1 to 48 h postsurfactant in GLSE and Beractant groups

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Source: PubMed

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