U.S. Department of Health & Human Services
Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW)
Overview
The Research Need
Newborns exposed to opioids in the womb are at risk for a condition called neonatal opioid withdrawal syndrome (NOWS) or neonatal abstinence syndrome. NOWS symptoms can include tremors; excessive crying and irritability; and problems with sleeping, feeding, and breathing.
From 2010 to 2017, the estimated rate of neonatal abstinence syndrome increased from 4.0 to 7.3 per 1,000 birth hospitalizations. [1] Little is known about the long-term effects of this condition, and few standard, evidence-based treatments exist for NOWS.
About the ACT NOW Program
The Advancing Clinical Trials in Neonatal Opioid Withdrawal Syndrome (ACT NOW) Program aims to inform the clinical care of infants who are exposed to opioids in the womb. The ACT NOW Program combines the efforts of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network and the Institutional Development Award (IDeA) States Pediatric Clinical Trials Network (ISPCTN) to include a geographically and racially diverse population. The ACT NOW Program was launched in 2017 when investigators in the ACT NOW Program assessed the variation in care for NOWS in 30 research hospitals across the United States. [2] The management approaches surveyed by the ACT NOW investigators were then used to develop research protocols for large-scale studies in the ACT NOW Program.
[1] Hirai AH, et al. Neonatal Abstinence Syndrome and Maternal Opioid-Related Diagnoses in the US, 2010-2017. JAMA. 2021 Jan 12;325(2):146-155. doi: 10.1001/jama.2020.24991.
[2] Young LW, et al. Site-Level Variation in the Characteristics and Care of Infants With Neonatal Opioid Withdrawal. Pediatrics. 2021 Jan;147(1):e2020008839. doi: 10.1542/peds.2020-008839.
In the current phase of the Program, ACT NOW clinical trials will provide an evidence base for the clinical care of infants with NOWS to help inform medical practice and health policy.
- The ACT NOW Eat, Sleep, Console (ESC) Clinical Trial. ESC is a strategy to treat infants with NOWS that prioritizes non-pharmacologic care over the use of opioids. This ACT NOW trial will compare infant outcomes before ESC was implemented at hospitals and after it was implemented.
- The ACT NOW Trial to Shorten Pharmacologic Treatment of Newborns with NOWS (Weaning Trial). The Weaning trial will compare rapid with slow opioid weaning management among neonates with NOWS treated with morphine or methadone.
- The ACT NOW Longitudinal Study. The longitudinal study will look at MRI findings and other data in infants with and without NOWS to examine the impact of antenatal opioid exposure and NOWS on childhood brain structure and connectivity and on medical, developmental, and behavioral trajectories in early childhood. The study will also identify risk factors for adverse sequelae to optimize neurodevelopmental, behavioral, and family outcomes.
In the next phase of the Program, ACT NOW investigators will plan and conduct a multi-center, randomized controlled clinical trial that further investigates how to optimize care for infants exposed to opioids in utero, while also taking into account other types of non-drug therapies, such as behavioral interventions. The goal is to generate results that can inform clinical practice guidelines and give newborns with NOWS the best start possible.
Program Details
Through the Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative®, NIH has funded RTI International and the Duke Clinical Research Institute to support the ACT NOW clinical trials. In its next phase, the ACT NOW Program will establish a research consortium using the infrastructure and longstanding collaborations of four of the clinical sites with the highest enrollments of NOWS infants and the data coordinating center of the NICHD Neonatal Research Network. Since 2018, HEAL has awarded $47.6 million for ACT NOW.
- Research Triangle Institute – North Carolina and California
- University of Alabama at Birmingham – Alabama
- University of Arkansas for Medical Sciences – Arkansas
- Thomas Jefferson University – Pennsylvania
- University of New Mexico Health Science Center – New Mexico
- Children’s Hospital of Philadelphia – Pennsylvania
- Cincinnati Children’s Hospital Medical Center – Ohio
- University of Louisville – Kentucky
- Indiana University-Purdue University at Indianapolis – Kentucky
- RTI International – North Carolina
- Duke University – North Carolina
- RTI International – North Carolina