Withdrawal Clinical Trial
Official title:
Sublingual Buprenorphine Treatment for Neonatal Abstinence Syndrome - Pilot Study
Summary: There have been two published RCTs showing efficacy of buprenorphine treatment for NAS. However these trials excluded an estimated 22-47% of infants requiring pharmacologic treatment; those infants born to mothers with co-dependence on an opiate and a benzodiazepine. Although there are concerns, we anticipate that buprenorphine will be safe in this population. If it is safe, we can include these infants in the large double blind, double-dummy buprenorphine and clonidine vs. morphine and clonidine trial. If on the other hand, these infants have respiratory depression or other adverse events when buprenorphine is given, it will be important to report this study and caution the use of buprenorphine in these infants
The Problem: Infants who are born to mothers taking or abusing opiates frequently suffer
from neonatal abstinence syndrome (NAS) after birth. They often have withdrawal symptoms
which can be life threatening if untreated. The American Academy of Pediatrics recommends
opioid replacement for the treatment of these symptoms in newborns. Buprenorphine (BNP) has
gained widespread use in the treatment of adult opioid dependence. One of the reasons BNP is
so appealing is because of its safety profile in comparison to the other drugs in its class
(opiates). It has less respiratory depression and a lower level of physical dependence than
the other opioids. BNP has recently been trialed, in its sublingual form, as a treatment for
newborns with NAS. In two trials by the same group, there was a significant reduction in
both the length of treatment and in-patient hospital days in infants treated with BNP in
comparison to infants treated with morphine.
In both of these studies, mother/infant pairs were excluded if the mother was dual dependent
on opiates and benzodiazepines (BZDs). This is not an insignificant population. BZDs are
frequently prescribed during pregnancy to treat anxiety and panic disorder in women who are
taking methadone or BNP for opioid replacement therapy. BZDs are also common drugs of abuse.
It has been estimated that 22-47% of mothers whose infants are diagnosed with NAS used both
BZDs and opiates during the pregnancy. These infants have a protracted NAS with longer
hospitalization in comparison to infants exposed to an opioid alone. There are conflicting
reports in the literature regarding the safety of concomitant use of BNP and BZDs. In both
adults and children the combination of BNP and BZD prolongs respiratory depression in
non-drug abusers. In addition, autopsy findings in six adults who were drug abusers were
linked to concomitant use of BNP and BZD by analysis at autopsy. On the other hand in adult
tapering trials comparing BNP with methadone in dual-dependent adults there were no adverse
events in the BNP group, opiate withdrawal scores were lower and the adults were more likely
to complete treatment. Thus while treatment of NAS with BNP may be desirable and efficacious
in opiate tapering protocols, it is imperative that we look specifically at this group of
infants with dual exposure to opioids and BZDs. This is a single site, un-blinded
observational safety study. Study participants will be recruited from eligible participants
who are born at Bayfront Medical Center Baby Place and subsequently admitted to the neonatal
intensive care unit (NICU) at All Children's' Hospital (ACH) for treatment of NAS. Data from
this pilot safety trial will be used to apply for NIH funding to conduct a large randomized
double-blind trial to determine the efficacy of BNP versus morphine for the treatment of
NAS.
The Research Hypothesis: BNP can be used safely to treat NAS in the subgroup of infants
whose mothers were taking both an opiate and a BZD in the week prior to delivery.
The Importance of the Research: BNP is emerging as a "safer" and more efficient drug for
adult detoxification and maintenance programs and is showing promise for the treatment of
neonatal abstinence syndrome (NAS). In the most recent published trial comparing BNP to
morphine in infants with NAS, the length of stay (LOS) was decreased by 40% in the BNP group
(from an average of 38 days in the morphine group to 23 days in the BNP group). No major
adverse effects were reported in either treatment group. As is common in early trials, the
experimental group was restricted - specifically maternal BZD use was an exclusion criteria.
The rational given was that length of stay is known to be longer for infants whose mothers
were also using BZDs. However, this is not an insignificant population. It has been reported
that 22-47% of opiate users are co-using BZDs. At ACH, the incidence of infants exposed to
both classes of drugs has ranged from 15-35%. Before BNP becomes the standard of care it is
important to look closely at this group of infants and either caution the use of BNP or
demonstrate its safety. This pilot trial is designed to determine if infants who have dual
in-utero exposures to opiates and BZDs can be safely treated with BNP.
;
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT04550754 -
Evaluation of the Management of Tramadol Use Disorders
|
||
Recruiting |
NCT04610476 -
Impact of Tapering Immunosuppressants on Maintaining Minimal Disease Activity in Adult Subjects With Psoriatic Arthritis
|
Phase 3 | |
Recruiting |
NCT06066996 -
Evaluation of the Electronic Cigarette Withdrawal Syndrome
|
Early Phase 1 | |
Completed |
NCT01431326 -
Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care
|
||
Completed |
NCT04105712 -
The Biobehavioral Impact of Diet Quality on Affect and Craving
|
N/A | |
Completed |
NCT03376308 -
Evaluation of the Effect of Venous Diameter Measurement by Ultrasonography on Pain and Withdrawal Response
|
N/A | |
Recruiting |
NCT05964738 -
Effect of Diuretics Withdrawal in Chronic Heart Failure With Reduced Ejection Fraction
|
Phase 2 | |
Completed |
NCT03973801 -
Feasibility of Auricular Acupressure as an Adjunct Treatment for Neonatal Abstinence Syndrome (NAS)
|
N/A | |
Completed |
NCT03462797 -
Opioid Physiology Project
|
||
Completed |
NCT01818895 -
Terminal Weaning of Mechanical Ventilation or Extubation in Anticipation of Death in the Intensive Care Unit
|
N/A |