Clonidine vs Morphine for Neonatal Abstinence Syndrome

Overseen By Rupinder Kaur, MD

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: The Cooper Health System

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: Up to 100 days

69 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to show non-inferiority between two medications used for medical treatment of withdrawal seen in Neonatal Abstinence Syndrome (NAS), Clonidine and Morphine Sulfate (used in routine care) on length of treatment for NAS .

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications.

What data supports the effectiveness of the drug clonidine for treating Neonatal Abstinence Syndrome?

Research suggests that clonidine, when added to standard opioid treatment, can reduce the number of treatment days and the dose of opioid needed for infants with Neonatal Abstinence Syndrome. However, there is a risk of symptoms returning after stopping the opioid, so careful planning is needed when discharging patients. ^{1 2 3 4 5}

Is clonidine safe for treating neonatal abstinence syndrome?

Clonidine has been used in infants with neonatal abstinence syndrome without toxic side effects at certain doses, suggesting it may be safe for this condition. However, its use remains investigational, and more research is needed to confirm its safety compared to other treatments. ^{3 6 7 8 9}

How is the drug clonidine unique in treating neonatal abstinence syndrome?

Clonidine is unique in treating neonatal abstinence syndrome because it works as an alpha 2-adrenergic agonist, which helps reduce withdrawal symptoms by calming the nervous system. Unlike traditional treatments like morphine, clonidine does not have the same risk of dependency and has shown promise in reducing the duration of morphine therapy when used as an adjunctive treatment. ^{1 2 4 6 10}

Research Team

Alla Kushnir, MD

Principal Investigator

The Cooper Health System

Eligibility Criteria

This trial is for newborns born at Cooper University Hospital, who are at least 35 weeks gestational age and show withdrawal symptoms from substances their mothers used during pregnancy. These babies should not have congenital anomalies or major medical conditions like blood pressure instability.

Inclusion Criteria

I do not have any birth defects or brain conditions.

I am at least 35 weeks into my pregnancy.

Mothers admitted to using illicit substances or prescription medications (which can result in withdrawal symptoms) while pregnant and/or had a positive urine drug screen during pregnancy

Exclusion Criteria

My blood pressure frequently changes.

Major medical conditions

Infants with major congenital abnormalities

Timeline

Screening

Participants are screened for eligibility to participate in the trial

72 hours to 5 days

In-hospital observation

Treatment

Infants receive either Clonidine or Morphine for NAS treatment, with potential addition of Phenobarbital as rescue therapy

Up to 100 days

Continuous in-hospital monitoring

Follow-up

Participants are monitored for developmental outcomes until 2 years of age

24 months

Contact at 6, 12, and 24 months for ASQ

Treatment Details

Interventions

• Clonidine
• Morphine Sulfate

Trial Overview The study compares Clonidine with Morphine Sulfate to see if Clonidine can shorten the hospital stay and treatment duration for Neonatal Abstinence Syndrome (NAS), which affects babies withdrawing from exposure to drugs in the womb.

Participant Groups

Group I: Clonidine Experimental Treatment 1 Intervention

Clonidine at 0.38 mcg/kg/dose every 3 hours or 0.5 mcg/kg/dose every 4 hours

Group II: Morphine Active Control 1 Intervention

Morphine Sulfate at 0.03 mg/kg/dose every 3 hours or 0.04 mg/kg/dose every 4 hours

Clonidine is already approved in United States, European Union for the following indications:

Approved in United States as Catapres for:

• Hypertension
• ADHD
• Severe cancer pain
• Withdrawal symptoms from various substances
• Diagnosis of pheochromocytoma
• Prevention of migraines

Approved in European Union as Catapres for:

• Hypertension
• ADHD
• Severe cancer pain
• Withdrawal symptoms from various substances
• Diagnosis of pheochromocytoma
• Prevention of migraines

Who Is Running the Clinical Trial?

The Cooper Health System

Lead Sponsor

Trials

82

Recruited

35,600+

Findings from Research

Clonidine extended-release and clonidine have been found to be effective in treating ADHD symptoms in children and adolescents, based on a review of ten clinical trials, with nine showing positive results.

Both forms of clonidine were reported to be well tolerated, with common side effects including drowsiness and fatigue, but there are concerns about potential serious cardiac side effects, highlighting the need for further research on long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of clonidine and clonidine extended-release in the treatment of children and adolescents with attention deficit and hyperactivity disorders. Ming, X., Mulvey, M., Mohanty, S., et al.[2021]

A compounded oral clonidine hydrochloride powder (0.2 mg/g) maintained its stability and quality for 120 days under controlled storage conditions, ensuring consistent dosing for pediatric patients.

No degradation products were detected, and the clonidine content remained within the acceptable range (90.0% to 110.0% of initial content), indicating that the compounded formulation is safe and effective for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stability of clonidine hydrochloride in an oral powder form compounded for pediatric patients in Japan. Saito, J., Hanawa, T., Matsumoto, T., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Emerging therapies for the treatment of neonatal abstinence syndrome. [2022]

2. Norway pubmed.ncbi.nlm.nih.gov

Treatment of neonatal abstinence syndrome with clonidine and chloral hydrate. [2013]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Behavioral evaluation of rats prenatally exposed to the adrenergic agonists clonidine and lofexidine. [2014]

4. United States pubmed.ncbi.nlm.nih.gov

Clonidine versus phenobarbital as adjunctive therapy for neonatal abstinence syndrome. [2021]

5. Australia pubmed.ncbi.nlm.nih.gov

Does the addition of clonidine to opioid therapy improve outcomes in infants with Neonatal Abstinence Syndrome? [2022]

6. Ireland pubmed.ncbi.nlm.nih.gov

Clonidine treatment of neonatal narcotic abstinence syndrome. [2019]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of clonidine and clonidine extended-release in the treatment of children and adolescents with attention deficit and hyperactivity disorders. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Stability study of a clonidine oral solution in a novel vehicle designed for pediatric patients. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Stability of clonidine hydrochloride in an oral powder form compounded for pediatric patients in Japan. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Efficacy of clonidine versus phenobarbital in reducing neonatal morphine sulfate therapy days for neonatal abstinence syndrome. A prospective randomized clinical trial. [2014]