Effects of<i>My</i>o-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants &amp;lt;28 Weeks’ Gestational Age
Authors: Dale L. Phelps, Kristi L. Watterberg, Tracy L. Nolen, Carol A. Cole, C. Michael Cotten, William Oh, Brenda B. Poindexter, Kristin M. Zaterka-Baxter, Abhik Das, Conra Backstrom Lacy, Ann Marie Scorsone, Michele C. Walsh, Edward F. Bell, Kathleen A. Kennedy, Kurt Schibler, Gregory M. Sokol, Matthew M. Laughon, Satyanarayana Lakshminrusimha, William E. Truog, Meena Garg, Waldemar A. Carlo, Abbot R. Laptook, Krisa P. Van Meurs, David P. Carlton, Amanda Graf, Sara B. DeMauro, Luc P. Brion, Seetha Shankaran, Faruk H. Orge, Richard J. Olson, Helen Mintz-Hittner, Michael B. Yang, Kathryn M. Haider, David K. Wallace, Mina Chung, Denise Hug, Irena Tsui, Martin S. Cogen, John P. Donahue, Michael Gaynon, Amy K. Hutchinson, Don L. Bremer, Graham Quinn, Yu-Guang He, William R. Lucas, Timothy W. Winter, Stephen D. Kicklighter, Kartik Kumar, Patricia R. Chess, Tarah T. Colaizy, Anna Marie Hibbs, Namasivayam Ambalavanan, Heidi M. Harmon, Elisabeth C. McGowan, Rosemary D. Higgins
Journal: JAMA (2018)

<h3>Importance</h3> Previous studies of<i>myo</i>-inositol in preterm infants with respiratory distress found reduced severity of retinopathy of prematurity (ROP) and less frequent ROP, death, and intraventricular hemorrhage. However, no large trials have tested its efficacy or safety. <h3>Objective</h3> To test the adverse events and efficacy of<i>myo</i>-inositol to reduce type 1 ROP among infants younger than 28 weeks' gestational age. <h3>Design, Setting, and Participants</h3> Randomized clinical trial included 638 infants younger than 28 weeks' gestational age enrolled from 18 neonatal intensive care centers throughout the United States from April 17, 2014, to September 4, 2015; final date of follow-up was February 12, 2016. The planned enrollment of 1760 participants would permit detection of an absolute reduction in death or type 1 ROP of 7% with 90% power. The trial was terminated early due to a statistically significantly higher mortality rate in the<i>myo-</i>inositol group. <h3>Interventions</h3> A 40-mg/kg dose of<i>myo</i>-inositol was given every 12 hours (initially intravenously, then enterally when feeding; n = 317) or placebo (n = 321) for up to 10 weeks. <h3>Main Outcomes and Measures</h3> Type 1 ROP or death before determination of ROP outcome was designated as unfavorable. The designated favorable outcome was survival without type 1 ROP. <h3>Results</h3> Among 638 infants (mean, 26 weeks' gestational age; 50% male), 632 (99%) received the trial drug or placebo and 589 (92%) had a study outcome. Death or type 1 ROP occurred more often in the<i>myo</i>-inositol group vs the placebo group (29% vs 21%, respectively; adjusted risk difference, 7% [95% CI, 0%-13%]; adjusted relative risk, 1.41 [95% CI, 1.08-1.83],<i>P</i> = .01). All-cause death before 55 weeks' postmenstrual age occurred in 18% of the<i>myo</i>-inositol group and in 11% of the placebo group (adjusted risk difference, 6% [95% CI, 0%-11%]; adjusted relative risk, 1.66 [95% CI, 1.14-2.43],<i>P</i> = .007). The most common serious adverse events up to 7 days of receiving the ending dose were necrotizing enterocolitis (6% for<i>myo</i>-inositol vs 4% for placebo), poor perfusion or hypotension (7% vs 4%, respectively), intraventricular hemorrhage (10% vs 9%), systemic infection (16% vs 11%), and respiratory distress (15% vs 13%). <h3>Conclusions and Relevance</h3> Among premature infants younger than 28 weeks' gestational age, treatment with<i>myo</i>-inositol for up to 10 weeks did not reduce the risk of type 1 ROP or death vs placebo. These findings do not support the use of<i>myo</i>-inositol among premature infants; however, the early termination of the trial limits definitive conclusions.