Trial Outcomes & Findings for Methadone Demonstration Project With Neonatal Intensive Care Unit Infants Diagnosed With Neonatal Abstinence Syndrome (NCT NCT03134703)

Results Overview

Compare the LOS of Neonatal Intensive Care Unit (NICU) infants with Neonatal Abstinence Syndrome (NAS) treated with methadone with historical data and a comparison group of NICU NAS infants treated with a different narcotic agent.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

11 participants

Primary outcome timeframe

25 days

Results posted on

2023-07-03

Participant Flow

Participant milestones

Participant milestones
Measure	Methadone Treatment Group NAS infants treated for withdrawal symptoms with methadone Methadone: Infants in the Methadone Treatment Group will receive the study drug, methadone, instead of morphine to treat withdrawal symptoms from Neonatal Abstinence Syndrome (NAS)	Comparison Group NAS infants treated for withdrawal symptoms with morphine (standard of care at Johns Hopkins All Children's Hospital) Morphine: Infants in the Comparison Group will receive standard of care narcotic (morphine) to treat withdrawal symptoms from Neonatal Abstinence Syndrome (NAS)
Overall Study STARTED	6	5
Overall Study COMPLETED	0	3
Overall Study NOT COMPLETED	6	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Methadone Demonstration Project With Neonatal Intensive Care Unit Infants Diagnosed With Neonatal Abstinence Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Methadone Treatment Group n=6 Participants NAS infants treated for withdrawal symptoms with methadone Methadone: Infants in the Methadone Treatment Group will receive the study drug, methadone, instead of morphine to treat withdrawal symptoms from Neonatal Abstinence Syndrome (NAS)	Comparison Group n=5 Participants NAS infants treated for withdrawal symptoms with morphine (standard of care at Johns Hopkins All Children's Hospital) Morphine: Infants in the Comparison Group will receive standard of care narcotic (morphine) to treat withdrawal symptoms from Neonatal Abstinence Syndrome (NAS)	Total n=11 Participants Total of all reporting groups
Age, Continuous	1.5 Days n=5 Participants	10.4 Days n=7 Participants	5.5 Days n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: 25 days

Population: Study closed prematurely due to poor accrual. There were 3 screen fails (did not receive study drug) in the methadone treatment group, therefore LOS was not calculated for those participants.

Compare the LOS of Neonatal Intensive Care Unit (NICU) infants with Neonatal Abstinence Syndrome (NAS) treated with methadone with historical data and a comparison group of NICU NAS infants treated with a different narcotic agent.

Outcome measures

Outcome measures
Measure	Methadone Treatment Group n=3 Participants NAS infants treated for withdrawal symptoms with methadone Methadone: Infants in the Methadone Treatment Group will receive the study drug, methadone, instead of morphine to treat withdrawal symptoms from Neonatal Abstinence Syndrome (NAS)	Comparison Group n=5 Participants NAS infants treated for withdrawal symptoms with morphine (standard of care at Johns Hopkins All Children's Hospital) Morphine: Infants in the Comparison Group will receive standard of care narcotic (morphine) to treat withdrawal symptoms from Neonatal Abstinence Syndrome (NAS)
Length of Stay (LOS)	11.3 days Interval 9.0 to 15.0	16.2 days Interval 6.0 to 25.0

SECONDARY outcome

Timeframe: inpatient and at 6-8 weeks of age

Population: Data analysis was not completed. Results shown below are means for each group, note that many participants replied on the extremes of the answer range (e.g. always or never), which yields very low total scores for each factor.

The Postpartum Bonding Questionnaire (PBQ) is a self-rating questionnaire designed to detect disorders of the mother-infant relationship. The questionnaire has 25 statements, each with six alternative responses ranging from 0 (always) to 5 (never). For the PBQ, scores are summated for each factor, with a high score indicating concern for bonding. The PBQ yields a total score between 0 to 125. Positive responses are scored from 0 ('always') to 5 ('never'). Negative responses, are scored from 5 ('always') to 0 ('never'). Factor 1 (impaired bonding) is based on 12 questions, with a score range 0-60 (0-11=normal; 12 \& above=high). Factor 2 (rejection \& anger) is based on 7 questions with a score range 0-35 (0-16=normal; 17 \& above=high). Factor 3 (anxiety about care) is based on 4 questions with a score range 0-20 (0-9=normal; 10 \& above =high). Factor 4 (risk of abuse) is based on 2 questions, with a score range 0-10 (0-2=normal; 3 \& above =high).

Outcome measures

Outcome measures
Measure	Methadone Treatment Group n=5 Participants NAS infants treated for withdrawal symptoms with methadone Methadone: Infants in the Methadone Treatment Group will receive the study drug, methadone, instead of morphine to treat withdrawal symptoms from Neonatal Abstinence Syndrome (NAS)	Comparison Group n=5 Participants NAS infants treated for withdrawal symptoms with morphine (standard of care at Johns Hopkins All Children's Hospital) Morphine: Infants in the Comparison Group will receive standard of care narcotic (morphine) to treat withdrawal symptoms from Neonatal Abstinence Syndrome (NAS)
Maternal Bonding Measured With The Postpartum Bonding Questionnaire (PBQ) Factor 2 inpatient	0 score on a scale Interval 0.0 to 0.0	0 score on a scale Interval 0.0 to 0.0
Maternal Bonding Measured With The Postpartum Bonding Questionnaire (PBQ) Factor 4 inpatient	0 score on a scale Interval 0.0 to 0.0	0 score on a scale Interval 0.0 to 0.0
Maternal Bonding Measured With The Postpartum Bonding Questionnaire (PBQ) Factor 2 6-8 weeks	0 score on a scale Interval 0.0 to 0.0	1 score on a scale Interval 0.0 to 2.0
Maternal Bonding Measured With The Postpartum Bonding Questionnaire (PBQ) Factor 3 6-8 weeks	0 score on a scale Interval 0.0 to 0.0	2.5 score on a scale Interval 2.0 to 3.0
Maternal Bonding Measured With The Postpartum Bonding Questionnaire (PBQ) Factor 1 inpatient	0 score on a scale Interval 0.0 to 0.0	0.4 score on a scale Interval 0.0 to 2.0
Maternal Bonding Measured With The Postpartum Bonding Questionnaire (PBQ) Factor 3 inpatient	0.6 score on a scale Interval 0.0 to 1.0	1 score on a scale Interval 0.0 to 2.0
Maternal Bonding Measured With The Postpartum Bonding Questionnaire (PBQ) Factor 1 6-8 weeks	1 score on a scale Interval 1.0 to 1.0	0.5 score on a scale Interval 0.0 to 1.0
Maternal Bonding Measured With The Postpartum Bonding Questionnaire (PBQ) Factor 4 6-8 weeks	0 score on a scale Interval 0.0 to 0.0	0 score on a scale Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: While inpatient and at 6-8 weeks of age

Population: Data analysis was not completed. Results shown below are average scores on the EPDS scale for each group. 9 participants completed the EPDS while in patient, and 4 participants completed the questionnaire at the 6-8 weeks time point.

The Edinburgh Postnatal Depression Scale (EPDS) was developed for screening postpartum women in outpatient, home visiting settings, or at the 6-8 week postpartum examination. The EPDS is a 10-item questionnaire with responses scored 0, 1, 2, or 3 according to increased severity of the symptom. The maximum total score is 30 while the minimum score is 0. A score of 10 or greater, as well as any answer choice other than "never" on question #10 (suicidal thoughts) of the EPDS are indicative of depressive symptomatology.

Outcome measures

Outcome measures
Measure	Methadone Treatment Group n=4 Participants NAS infants treated for withdrawal symptoms with methadone Methadone: Infants in the Methadone Treatment Group will receive the study drug, methadone, instead of morphine to treat withdrawal symptoms from Neonatal Abstinence Syndrome (NAS)	Comparison Group n=5 Participants NAS infants treated for withdrawal symptoms with morphine (standard of care at Johns Hopkins All Children's Hospital) Morphine: Infants in the Comparison Group will receive standard of care narcotic (morphine) to treat withdrawal symptoms from Neonatal Abstinence Syndrome (NAS)
Maternal Depression Measured With The Edinburgh Postnatal Depression Scale (EPDS) EPDS inpatient	0.3 score on a scale Interval 0.0 to 1.0	7.2 score on a scale Interval 1.0 to 20.0
Maternal Depression Measured With The Edinburgh Postnatal Depression Scale (EPDS) EPDS 6-8 weeks	10 score on a scale Interval 10.0 to 10.0	5.3 score on a scale Interval 1.0 to 14.0

SECONDARY outcome

Timeframe: Within 30 days of discharge

Population: Readmissions to the hospital within 30 days for NAS-related reasons.

Number of hospital readmissions

Outcome measures

Outcome measures
Measure	Methadone Treatment Group n=4 Participants NAS infants treated for withdrawal symptoms with methadone Methadone: Infants in the Methadone Treatment Group will receive the study drug, methadone, instead of morphine to treat withdrawal symptoms from Neonatal Abstinence Syndrome (NAS)	Comparison Group n=5 Participants NAS infants treated for withdrawal symptoms with morphine (standard of care at Johns Hopkins All Children's Hospital) Morphine: Infants in the Comparison Group will receive standard of care narcotic (morphine) to treat withdrawal symptoms from Neonatal Abstinence Syndrome (NAS)
Readmission to Hospital	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 30 days of age

Population: Study closed prematurely due to poor accrual and no analysis was completed. Incidence of providing breast milk at 30 days was not collected.

Compare the incidence of providing breast milk (\> 50% of nutritional needs) at 30 days of age between methadone treated and non-treated infants

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4, 8 and 12 months of age

Population: Infant development assessed only on those participants who received study drug (methadone arm). 3 participants completed the ASQ at 4 months, 1 participant at 8 months, and 1 participant at 12 months.

Assess the age appropriate infant development at 4, 8 and 12 months of age among the methadone treatment group using the Ages and Stages-based questionnaires (ASQ). The questionnaires are screening tools designed to identify infants at risk for developmental delays through caregivers' provision of quantitative information regarding their infant's development. In the ASQ, higher scores indicate more positive outcomes. The ASQ covers 5 areas of development: communication, gross motor, fine motor, problem solving, and personal-social. Scores for each area should fall between 0-60. Scoring: 0-30 = further assessment with a professional may be needed 30-40 = learning activities \& monitoring are indicated 45-60 = child development appears to be on schedule

Outcome measures

Outcome measures
Measure	Methadone Treatment Group n=3 Participants NAS infants treated for withdrawal symptoms with methadone Methadone: Infants in the Methadone Treatment Group will receive the study drug, methadone, instead of morphine to treat withdrawal symptoms from Neonatal Abstinence Syndrome (NAS)	Comparison Group NAS infants treated for withdrawal symptoms with morphine (standard of care at Johns Hopkins All Children's Hospital) Morphine: Infants in the Comparison Group will receive standard of care narcotic (morphine) to treat withdrawal symptoms from Neonatal Abstinence Syndrome (NAS)
Infant Development Communication at 4m	51.7 score on a scale Interval 45.0 to 60.0	—
Infant Development Fine motor at 4m	56.7 score on a scale Interval 55.0 to 60.0	—
Infant Development Problem solving at 4m	56.7 score on a scale Interval 50.0 to 60.0	—
Infant Development Communication at 8m	60 score on a scale Interval 60.0 to 60.0	—
Infant Development Gross motor at 8m	50 score on a scale Interval 50.0 to 50.0	—
Infant Development Fine motor at 8m	50 score on a scale Interval 50.0 to 50.0	—
Infant Development Problem solving at 8m	55 score on a scale Interval 55.0 to 55.0	—
Infant Development Personal-social at 8m	50 score on a scale Interval 50.0 to 50.0	—
Infant Development Communication at 12m	50 score on a scale Interval 50.0 to 50.0	—
Infant Development Gross motor at 12m	40 score on a scale Interval 40.0 to 40.0	—
Infant Development Problem solving at 12m	50 score on a scale Interval 50.0 to 50.0	—
Infant Development Personal-social at 12m	40 score on a scale Interval 40.0 to 40.0	—
Infant Development Gross motor at 4m	56.7 score on a scale Interval 50.0 to 60.0	—
Infant Development Personal-social at 4m	60 score on a scale Interval 60.0 to 60.0	—
Infant Development Fine motor at 12m	60 score on a scale Interval 60.0 to 60.0	—

SECONDARY outcome

Timeframe: After accrual of the first 50% of participants & after accrual of the second 50% of participants, and at completion of the trial.

Population: Study closed prematurely due to poor accrual and no analysis was completed. Response percentage was not collected.

Determine the response percentage of mothers who are screened as eligible by PAR officials and who agree to participate in the demonstration project

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: After accrual of the first 50% of participants, after accrual of the second 50% of participants, and at completion of the trial.

Population: Study closed prematurely due to poor accrual and no analysis was completed. Drop out percentage was not collected.

Assess the drop out percentage of mothers who agree to participate but do not follow through with home discharge for continued care

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: After accrual of the first 50% of participants, after accrual of the second 50% of participants, and at completion of the trial

Population: Study closed prematurely due to poor accrual and no analysis was completed. Proportion of mothers data was not collected.

Quantitate the proportion of mothers who feel comfortable with home care of their infant at discharge

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: After accrual of the first 50% of participants, after accrual of the second 50% of participants, and at completion of the trial.

Population: Study closed prematurely due to poor accrual and no analysis was completed. Readiness of mothers was not assessed/collected.

Monitor the readiness of mothers to assess infant on 3 to 4 hours intervals while at home

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: After accrual of the first 50% of participants, after accrual of the second 50% of participants, and at completion of the trial.

Population: Study closed prematurely due to poor accrual and no analysis was completed. Compliance rate was not assessed/collected.

Determine the compliance rate with the Johns Hopkins All Children's Hospital (JHACH) pediatrician visits.

Outcome measures

Outcome data not reported

Adverse Events

Methadone Treatment Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Comparison Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Sandra Brooks, MD

Johns Hopkins All Children's Hospital

Phone: 727-767-4313

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place