Purpose:
This FOA invites applications for Clinical Centers to design and implement a multi-center, comparative effectiveness, randomized controlled trial (RCT) to assess the optimal pharmacological treatment for Neonatal Opioid Withdrawal Syndrome (NOWS).
A separate FOA (RFA-HD-21-032) will invite applications for Data Coordinating Center (DCC).
Information obtained from this study is expected to inform clinical practice guidelines and the care of infants with NOWS.
The funding for this initiative is provided from the Helping to End Addiction Long-term (HEAL) initiative (https://heal.nih.gov/).
Background:
At the 2018 National Prescription Drug Abuse and Heroin Summit, National Institutes of Health Director Francis S. Collins, M.D., Ph.D., announced the launch of the HEAL (Helping to End Addiction Long-term) Initiative, an aggressive, trans-agency effort to speed scientific solutions to stem the national opioid public health crisis. Part of this initiative is to evaluate treatments and long-term consequences of Neonatal Opioid Withdrawal Syndrome (NOWS).
Women and children bear a substantial part of the burden of the current opioid crisis in the United States. Hospitalizations for opioid use disorder in pregnant women more than quadrupled during 1999–2014. This is a significant public health concern, given that opioid exposure is associated with adverse maternal and neonatal outcomes, including preterm labor, stillbirth, NOWS, and maternal mortality. Cases of NOWS have increased 5-fold since 2004 – a baby is born suffering from opioid withdrawal approximately every 15 minutes, and recent data from the U.S. Pediatric Health Information System suggest an incidence of NOWS as high as 20 cases per 1000 live births (with a treatment cost of more than $560 million per year). In addition, not only can opioid use during pregnancy lead to NOWS, but both the mothers and babies may be at higher risk of opioid use and its consequences later in the life course, setting up intergenerational cycles of opioid overuse.
The Advancing Clinical Trials in Neonatal Opioid Withdrawal syndrome (ACT NOW) project’s Current Experience study found a wide variation in NOWS care practices, including pharmacologic agents, with no consensus as to which medication regimen is better. Currently, the most common first-line medications for NOWS are morphine and methadone; phenobarbital and clonidine are the most commonly used adjunct agents.
A meta-analysis published in 2019 suggested that buprenorphine may be the optimal pharmacologic treatment for infants with NOWS. However, the primary findings of this meta-analysis need to be interpreted with caution and properly conducted direct comparative-effectiveness studies are needed to inform clinical practice.
Unfortunately, findings from previous studies that compared different treatment medications for NOWS have been limited:
- Several studies were not blinded.
- No large studies have directly compared buprenorphine with methadone.
- All studies are limited by the choice of weaning protocol used for each medication. For example, studies comparing buprenorphine and morphine have been limited by use of particularly slow weaning approaches for morphine.
- Studies may be influenced by the preparation (e.g., containing alcohol) or route of administration (e.g., oral vs sublingual) of the medications.
- Few studies have either compared, or even controlled adequately for the use of adjunct medications.
- Few studies have controlled for varying use of non-pharmacologic therapies.
- Comparison studies have not adequately accounted for the possibility of differences in populations of infants being treated. For example, it is possible that buprenorphine may be preferable for infants of women using buprenorphine for medication-assisted treatment for opioid use disorder, whereas morphine or methadone may be better for infants of mothers actively using opioids.
To address these scientific gaps, a workshop supported by the HEAL initiative and addressing issues related to the treatment of infants with NOWS was held on August 24-25, 2020. Contents of the workshop are archived on the following website: https://heal.nih.gov/events/2020-buprenorphine-infants.
As such, this FOA invites applications for Clinical Centers to participate in a multi-center, large-scale RCT that directly compares morphine, methadone, and buprenorphine, and takes into account non-pharmacologic factors and adjunct therapies. The expected follow-up is at least 24 months. A separate FOA (RFA-HD-21-032) will provide support for a DCC to support these efforts. The goal is to generate results that can inform clinical practice guidelines.
Key Dates:
URL for more information:
https://grants.nih.gov/grants/guide/rfa-files/RFA-HD-21-031.html
Filed Under: Funding Opportunities