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Ondansetron to reduce neonatal opioid withdrawal severity a randomized clinical trial

Abstract

Objective

To determine if treatment with a 5-HT3 antagonist (ondansetron) reduces need for opioid therapy in infants at risk for neonatal opioid withdrawal syndrome (NOWS).

Study design

A multicenter, randomized, placebo controlled, double blind clinical trial of ninety (90) infants. The intervention arms were intravenous ondansetron or placebo during labor followed by a daily dose of ondansetron or placebo in infants for five days.

Results

Twenty-two (49%) ondansetron-treated and 26 (63%) placebo-treated infants required pharmacologic treatment (p > 0.05). The Finnegan score was lower in the ondansetron-treated group (4.6 vs. 5.6, p = 0.02). A non-significant trend was noted for the duration of hospitalization. There was no difference in need for phenobarbital or clonidine therapy, or total dose of morphine in the first 15 days of NOWS treatment.

Conclusions

Ondansetron treatment reduced the severity of NOWS symptoms; and there was an indication that it could reduce the length of stay.

Clinical Trial Registration

Clinicaltrials.gov NCT01965704

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Fig. 1: Study design.
Fig. 2
Fig. 3: Secondary endpoints of total morphine dose and Finnegan score.
Fig. 4: This bar graph shows the number subjects in the placebo and ondansetron-treated groups with a duration of hospitalization for each indicated time.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We acknowledge the work of the following site principal investigators who assisted in the conduct of the study. Lori A. Devlin, MD (Univ. of Louisville), Ramasubbareddy Dhanireddy, MD (University of Tennessee Health Science Center), Ronald S. Cohen, MD (Lucile Packard Children’s Hospital), Camille M. Fung, MD (University of Utah), Juan E. Vargas, MD (University of California, San Francisco General Hospital). This trial was supported by National Institute of Drugs of Abuse (NIDA) R01 HD070795-06A1. Gary Petlz and Manhong Wu were also supported by a NIH/NIDA award 5U01DA04439902. The other authors received no additional funding. The NIH had no role in the design and conduct of the study.

Participating sites (number of subjects enrolled)

Thomas Jefferson University (42)

Johns Hopkins Bayview Medical Center (31)

Santa Clara Valley Medical Center (13)

University of Louisville (4)

University of Tennessee Health Science Center (3)

Lucile Packard Children’s Hospital (2)

University of Utah (2)

University of California, San Francisco General Hospital (1)

Author information

Authors and Affiliations

Authors

Contributions

GP conceptualized and designed the study, carried out the initial analyses, assisted with the initial draft, and reviewed and revised the manuscript. WKK drafted the initial manuscript, collected data, carried out the initial analyses, and reviewed and revised the manuscript. MW conducted statistical analysis, generated figures and tables, assisted with the initial draft, and reviewed and revised the manuscript. LMJ and SA-J collected data, contributed to the initial analyses, and reviewed and revised the manuscript. DD and SS, and CC coordinated and supervised data collection and review, contributed to the analyses, and reviewed and revised the manuscript. MW developed and conducted the analytical assay, and reviewed and revised the manuscript. BG, PJ, CA, and SK collected data, and reviewed and revised the manuscript

Corresponding author

Correspondence to Gary Peltz.

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The authors declare no competing interests.

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Peltz, G., Jansson, L.M., Adeniyi-Jones, S. et al. Ondansetron to reduce neonatal opioid withdrawal severity a randomized clinical trial. J Perinatol 43, 271–276 (2023). https://doi.org/10.1038/s41372-022-01487-2

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