Clonidine as Adjunct to Morphine for Neonatal Abstinence Syndrome

Clonidine as Adjunct to Morphine in the Management of Term and Near Term Infants With Neonatal Abstinence Syndrome

Status

Terminated

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03762317

Enrollment

Registered

2018-12-03

Start date

2018-04-30

Completion date

2018-12-12

Last updated

2023-02-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Neonatal Abstinence Syndrome

Brief summary

This is a prospective randomized double blinded study comparing the effect on duration of pharmacologic treatment and duration of hospital stay when using clonidine at 12 µg/kilogram/day as an adjunct to oral morphine as compared to morphine monotherapy in the management of term and near term infants with neonatal abstinence syndrome (NAS)

Detailed description

Neonatal abstinence syndrome (NAS) is an emerging epidemic and has lead to a tremendous increase in cost of medical care. Opioids are the mainstay of treatment for NAS although there are concerns about possible short-term and long-term effects including but not limited to adverse neurodevelopmental outcomes. Other drugs such as clonidine, phenobarbitone, methadone and buprenorphine have been evaluated to limit the postnatal exposure to opioids in these infants. Clonidine is an alpha 2 receptor and can lessen withdrawal manifestations. The addition of clonidine at 6 µg/kilogram/day to morphine in the management of NAS has been shown to reduce the duration of pharmacotherapy by about 27% in a previous study. A recent pilot study reported reduction of treatment duration for NAS with clonidine (12 µg/kilogram/day) monotherapy as compared to morphine monotherapy. The study reported no adverse effects in study subjects at the doses used in the study. The investigators hypothesize that there will be a minimum of 30% reduction in the treatment duration with 12 µg/kilogram/day clonidine used as adjuncts to standard morphine treatment as compared to morphine monotherapy in the management of term and near term infants with NAS

Interventions

DRUGClonidine

clonidine will be given at 12 mcg/kg/d to the experimental arm in addition to oral morphine

DRUGPlacebo

Placebo with volume similar to clonidine at 12 mcg/kg/d will be given to this arm in addition to oral morphine

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

36 Weeks to 45 Weeks

Healthy volunteers

Inclusion criteria

* Requiring neonatal intensive care unit (NICU) admission for management of neonatal abstinence syndrome * Gestational age greater than or equal to 36 weeks * Less than or equal to 48 hours of treatment with morphine for NAS

Exclusion criteria

* Presence of seizures * Congenital malformations, genetic syndromes or the presence of TORCH infections * Major medical problems * Heart rate and/or blood pressure instability

Design outcomes

Primary

Measure	Time frame	Description
Duration of Pharmacotherapy for NAS	From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days	The length of time in days from the initiation of pharmacotherapy on day 1 until the medication has been stopped

Secondary

Measure	Time frame	Description
Duration of Hospital Stay	From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days	Number of days spent in the hospital
Maximum Dose of Morphine Used	From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days	The maximum dose of morphine in mg/kg used for symptom control
Average Daily Dose of Oral Morphine Over Hospital Stay	From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days	The average daily dose of morphine used throughout study period in mg/kg/day
Total Number of Episodes of Heart Rate Variability (Heart Beats/Min)	From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days	Number of episodes of bradycardia (Heart rate \< 60/min for a minimum of 20 seconds and not associated with apnea or signs of reflux such as emesis, regurgitation of milk into the mouth or nose, arching while feeding, number of episodes of tachycardia (Heart rate \> 200/min) and not related to pain and/or agitation
Total Number of Episodes of Blood Pressure (mm of Hg) Variability	From beginning of morphine therapy during NICU admission until discharge from the hospital, up to 100 days	Number of episodes of hypotension (blood pressure \< 5th percentile for age) and hypertension (blood pressure \> 95th percentile for age)

Countries

United States

Participant flow

Pre-assignment details

This was a randomized blinded study where the HCMC research pharmacist assigned the randomization group and provided the study medication and placebo

Participants by arm

Arm	Count
Clonidine Clonidine is started at 6mcg/kg/day and increased to 12 mcg/kg/d for the duration of the study period Clonidine: clonidine will be given at 12 mcg/kg/d to the experimental arm in addition to oral morphine	5
Placebo Placebo solution will be given for the duration of the study period Placebo: Placebo with volume similar to clonidine at 12 mcg/kg/d will be given to this arm in addition to oral morphine	5
Total	10

Baseline characteristics

Characteristic	Placebo	Total	Clonidine
Age, Categorical <=18 years	5 Participants	10 Participants	5 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	0 Participants	0 Participants	0 Participants
Age, Continuous	37.4 weeks	38.3 weeks	39 weeks
Race (NIH/OMB) American Indian or Alaska Native	2 Participants	3 Participants	1 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) White	2 Participants	6 Participants	4 Participants
Region of Enrollment United States	5 participants	10 participants	5 participants
Sex: Female, Male Female	3 Participants	3 Participants	0 Participants
Sex: Female, Male Male	2 Participants	7 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 5	0 / 5
other Total, other adverse events	0 / 5	0 / 5
serious Total, serious adverse events	0 / 5	0 / 5

Outcome results

Primary

Duration of Pharmacotherapy for NAS

The length of time in days from the initiation of pharmacotherapy on day 1 until the medication has been stopped