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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01DA043519-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Drug Abuse (NIDA) | NIH |
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The long term goals of our research are to establish the best pharmacological treatment for NAS and determine how pharmacologic treatment of NAS affects long-term developmental outcomes. The objective of this application is to evaluate the effectiveness of clonidine as a treatment for neonates with NAS, in a randomized clinical trial. Our central hypothesis is that clonidine will effectively treat drug withdrawal manifestations in neonates.
In this current proposal, the research plan is based on our pilot study, which randomized infants with NAS to receive morphine or clonidine. The treatment groups were similar as to mean birth weight, gestational age, Apgar scores, and postnatal age at treatment. Infants enrolled had no other medical or surgical complications. Treatment was initiated per our NICU standard at the time, and will be continued in this protocol. Total LOS was shorter by about 1 week in the clonidine (mean of 15 days), compared to 21 days in the morphine group.
Aims and Objectives:
To determine whether the treatment of NAS with a non-opiate medication, clonidine, will be more effective than morphine
To determine whether treatment of NAS with clonidine will result in better early childhood outcomes than those treated with morphine • Compare the cognitive, motor and behavioral development of children in both treatment groups using the Bayley III Scales of Infant Development at 6 months, one and two years of age.
To build population pharmacokinetic/pharmacodynamic models and determine factors that affect exposure and response to morphine and clonidine
• Measure blood levels obtained at random times and correlate to Finnegan scores. The pharmacodynamics may help with understanding NAS medications and coping measures in babies.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Clonidine | Active Comparator | Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). |
|
| Morphine | Active Comparator | Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clonidine | Drug | 1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) | The summary scores from the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) give a measure of infant neurobehavior in the following areas (score range): habituation (1-9), regulation (2.20-7.50), attention (1.29-8.4), Handling (0-1), quality of movement (1.20-6.20), Non-optimal reflexes (0-12), Asymmetric reflexes (0-7), arousal (2.43-6.67), hypertonicity (0-8), hypotonicity (0-5.0), excitability (0-11), lethargy (0-11.0), and stress/abstinence (0-0.57). A higher score for each item means a higher level of the construct. For example, a higher score for hypertonicity means the infant is more hypertonic and higher score on hypotonicity means the infant is more hypotonic. No cut-off score published for normal or abnormal behavioral performance. | Baseline (5-10 days post natal age) and one-month post-natal age (between 4-6 weeks of age), or at discharge, whichever comes first. |
| Bayley Scales of Infant and Toddler Development Third Edition | Scores obtained Bayley Scales of Infant and Toddler Development Third Edition in the developmental domains of motor, cognitive, and language. This tool for measures of motor, cognitive, and language development is a series of standardized measurements and for each domain, the standardized scores have a mean of 100 and standard deviation of 15 with a range of 55-155 for cognitive and a range of 45-155 for language and motor (lower scores indicating greater impairment). Scores below 1 standard deviation (=or less than 84) is considered below normal. Scores above 1 standard deviation (over 115) represent higher than normal functioning in each domain. The score for each domain (motor, cognitive, and language functioning) represents the composite score. | 6 months of life |
| Bayley Scales of Infant and Toddler Development Third Edition | Scores obtained Bayley Scales of Infant and Toddler Development Third Edition in the developmental domains of motor, cognitive, and language. This tool for measures of motor, cognitive, and language development is a series of standardized measurements and for each domain, the standardized scores have a mean of 100 and standard deviation of 15 with a range of 55-155 for cognitive and a range of 45-155 for language and motor (lower scores indicating greater impairment). Scores below 1 standard deviation (=or less than 84) is considered below normal. Scores above 1 standard deviation (over 115) represent higher than normal functioning in each domain. The score for each domain (motor, cognitive, and language functioning) represents the composite score. |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of Treatment | Total number days of treatment | 60 days |
| Childhood Behavior Checklist 1.5-5 T-Scores | On the CBCL 1.5-5, T-scores, with a mean of 50 and a standard deviation of 10, are used to interpret results, with scores of 65 or higher indicating a clinical range, and scores between 60 and 64 suggesting a borderline clinical range. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Henrietta S Bada, MD MPH | University of Kentucky | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kentucky Children's Hospital | Lexington | Kentucky | 40536 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25624389 | Background | Bada HS, Sithisarn T, Gibson J, Garlitz K, Caldwell R, Capilouto G, Li Y, Leggas M, Breheny P. Morphine versus clonidine for neonatal abstinence syndrome. Pediatrics. 2015 Feb;135(2):e383-91. doi: 10.1542/peds.2014-2377. | |
| 14993525 | Background | Lester BM, Tronick EZ, LaGasse L, Seifer R, Bauer CR, Shankaran S, Bada HS, Wright LL, Smeriglio VL, Lu J. Summary statistics of neonatal intensive care unit network neurobehavioral scale scores from the maternal lifestyle study: a quasinormative sample. Pediatrics. 2004 Mar;113(3 Pt 2):668-75. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Clonidine | Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). Clonidine: 1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs. |
| FG001 | Morphine | Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). Morphine: Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Clonidine | Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). Clonidine: 1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs. |
| BG001 | Morphine |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Neurobehavioral Performance Summary Scores From the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) | The summary scores from the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) give a measure of infant neurobehavior in the following areas (score range): habituation (1-9), regulation (2.20-7.50), attention (1.29-8.4), Handling (0-1), quality of movement (1.20-6.20), Non-optimal reflexes (0-12), Asymmetric reflexes (0-7), arousal (2.43-6.67), hypertonicity (0-8), hypotonicity (0-5.0), excitability (0-11), lethargy (0-11.0), and stress/abstinence (0-0.57). A higher score for each item means a higher level of the construct. For example, a higher score for hypertonicity means the infant is more hypertonic and higher score on hypotonicity means the infant is more hypotonic. No cut-off score published for normal or abnormal behavioral performance. | Some babies were unable to be assessed in certain domains and therefore were not included in the total analyzed for that domain. | Posted | Mean | 95% Confidence Interval | score on a scale | Baseline (5-10 days post natal age) and one-month post-natal age (between 4-6 weeks of age), or at discharge, whichever comes first. |
Adverse events were collected from the time of consent until the subject was off study. For subjects who completed the entire study, the maximum amount of time for AE collection is 26 months from date of consent.
AEs were collected through the health system EMR and patient reports.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Clonidine | Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). Clonidine: 1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sustained tachycardia | Cardiac disorders | Systematic Assessment | >180 BPM for at least 3 hours |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Finnegan scores consecutively >8 | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Henrietta Bada | University of Kentucky | 8593231019 | henrietta.bada@uky.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Dec 17, 2024 | Mar 27, 2025 | Prot_SAP_ICF_002.pdf |
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| ID | Term |
|---|---|
| D009357 | Neonatal Abstinence Syndrome |
| D007232 | Infant, Newborn, Diseases |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
| ID | Term |
|---|---|
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| D003000 | Clonidine |
| D009020 | Morphine |
| ID | Term |
|---|---|
| D048288 | Imidazolines |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
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The study is intended to treat NAS using a randomized and double-blind study design to compare the use of opiate (morphine) or non-opiate (clonidine). Newborns meeting the study criteria for drug withdrawal and treatment will be randomized to receive one of the drugs (morphine, clonidine). Newborns requiring a second drug to help relieve the symptoms will be treated with phenobarbital for both groups. Randomization, blinding and dispensing will occur in the Investigational Drug Services Unit. Nursing personnel in the NICU will be masked to the treatment administered to each baby.
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The study will mask parents and child caregivers, and NICU nurses giving the drug, other personnel, residents and attending physicians, and research staff. Since initial dose is set using weight based-dosing, a physician's order can be entered in the electronic medical record to give the initial study drug with the infant's weight stated in the order. Increase in dosing will be ordered as to increase by 25% of initial dose or decrease of dose by 10% of maximum dose. During the pilot study, masking of treating personnel was maintained while the hospital pharmacist was the only person aware of which study drug the infant was receiving. The examiners for administration of the NNNS and the research nurse and research case worker will be masked to treatment received. Those seeing the infant in the clinic will also be masked to the treatment assignment. Morphine and clonidine are dispensed in identical appearance, color, smell, and volume.
|
| Morphine | Drug | Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs. |
|
|
| 1 year of life |
| Bayley Scales of Infant and Toddler Development Third Edition | Scores obtained Bayley Scales of Infant and Toddler Development Third Edition in the developmental domains of motor, cognitive, and language. This tool for measures of motor, cognitive, and language development is a series of standardized measurements and for each domain, the standardized scores have a mean of 100 and standard deviation of 15 with a range of 55-155 for cognitive and a range of 45-155 for language and motor (lower scores indicating greater impairment). Scores below 1 standard deviation (=or less than 84) is considered below normal. Scores above 1 standard deviation (over 115) represent higher than normal functioning in each domain. The score for each domain (motor, cognitive, and language functioning) represents the composite score. | 2 years of life |
| Ages and Stages Questionnaire Third Edition (ASQ-3) | The ASQ-3 is a developmental screening tool to assess developmental progress in children. Children are scored in the areas of communication, gross motor skills, fine motor skills, problem solving, and personal/social skills. The child's parent/guardian answers whether their child already does an activity (yes=10), sometimes does it (sometimes=5), or does not yet do it (not yet=0). The answers are then used to score each category. Each category is then broken down into whether the child falls above the cutoff (child development is on schedule), close to the cutoff (child development is slightly delayed and requires monitoring/intervention), or below the cutoff (delayed development and further assessment required). | 12 months of age |
| Ages and Stages Questionnaire Third Edition (ASQ-3) | The ASQ-3 is a developmental screening tool to assess developmental progress in children. Children are scored in the areas of communication, gross motor skills, fine motor skills, problem solving, and personal/social skills. The child's parent/guardian answers whether their child already does an activity (yes=10), sometimes does it (sometimes=5), or does not yet do it (not yet=0). The answers are then used to score each category. Each category is then broken down into whether the child falls above the cutoff (child development is on schedule), close to the cutoff (child development is slightly delayed and requires monitoring/intervention), or below the cutoff (delayed development and further assessment required). | 24 months |
| Childhood Behavior Checklist (CBCL) T-Scores | The CBCL/1.5-5 is validated for children ages 1.5 to 5 years old. It obtains caregivers' ratings of 113 behavior items. Scores are broken down into internalizing problems (scores range 29-100, normal is below 60), externalizing problems (scores range from 28-100, normal is below 60), and total problems (range is 28-100, normal is below 60). Items are scored on the following syndrome scales: Emotionally Reactive, Anxious/Depressed, Somatic Complaints, Withdrawn, Attention Problems, Aggressive Behavior, and Sleep Problems. Items are also scored on the following DSM-oriented scales: Affective Problems, Anxiety Problems, Pervasive Developmental Problems, Attention Deficit/Hyperactivity Problems, Stress Problems, Autism Spectrum Problems, and Oppositional Defiant Problems. The CBCL consists of 113 items, scored on a three-point Likert scale (0=absent, 1= occurs sometimes, 2=occurs often) | Once post discharge (between 18 months up to 24 months of age) |
| Once post discharge (between 18 months up to 24 months of age) |
Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). Morphine: Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | gestational age | Mean | Standard Deviation | weeks |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ID | Title | Description |
|---|
| OG000 | Clonidine | Babies randomized to clonidine will receive 1mcg/kg/dose (with a dosing interval of 3 or 4 hours). Clonidine: 1mcg/kg/dose (with a dosing interval of 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs. |
| OG001 | Morphine | Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). Morphine: Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs. |
|
|
| Primary | Bayley Scales of Infant and Toddler Development Third Edition | Scores obtained Bayley Scales of Infant and Toddler Development Third Edition in the developmental domains of motor, cognitive, and language. This tool for measures of motor, cognitive, and language development is a series of standardized measurements and for each domain, the standardized scores have a mean of 100 and standard deviation of 15 with a range of 55-155 for cognitive and a range of 45-155 for language and motor (lower scores indicating greater impairment). Scores below 1 standard deviation (=or less than 84) is considered below normal. Scores above 1 standard deviation (over 115) represent higher than normal functioning in each domain. The score for each domain (motor, cognitive, and language functioning) represents the composite score. | Participants may not have had the 6 month Bayley due to the participant being lost to follow up, or because of COVID-19 research restrictions. | Posted | Mean | Standard Deviation | score on a scale | 6 months of life |
|
|
|
| Primary | Bayley Scales of Infant and Toddler Development Third Edition | Scores obtained Bayley Scales of Infant and Toddler Development Third Edition in the developmental domains of motor, cognitive, and language. This tool for measures of motor, cognitive, and language development is a series of standardized measurements and for each domain, the standardized scores have a mean of 100 and standard deviation of 15 with a range of 55-155 for cognitive and a range of 45-155 for language and motor (lower scores indicating greater impairment). Scores below 1 standard deviation (=or less than 84) is considered below normal. Scores above 1 standard deviation (over 115) represent higher than normal functioning in each domain. The score for each domain (motor, cognitive, and language functioning) represents the composite score. | Participants may not have had the 12 month Bayley due to the participant being lost to follow up, or because of COVID-19 research restrictions. | Posted | Mean | Standard Deviation | score on a scale | 1 year of life |
|
|
|
| Primary | Bayley Scales of Infant and Toddler Development Third Edition | Scores obtained Bayley Scales of Infant and Toddler Development Third Edition in the developmental domains of motor, cognitive, and language. This tool for measures of motor, cognitive, and language development is a series of standardized measurements and for each domain, the standardized scores have a mean of 100 and standard deviation of 15 with a range of 55-155 for cognitive and a range of 45-155 for language and motor (lower scores indicating greater impairment). Scores below 1 standard deviation (=or less than 84) is considered below normal. Scores above 1 standard deviation (over 115) represent higher than normal functioning in each domain. The score for each domain (motor, cognitive, and language functioning) represents the composite score. | Participants may not have had the 24 month Bayley due to the participant being lost to follow up, or because of COVID-19 research restrictions. | Posted | Mean | Standard Deviation | score on a scale | 2 years of life |
|
|
|
| Primary | Ages and Stages Questionnaire Third Edition (ASQ-3) | The ASQ-3 is a developmental screening tool to assess developmental progress in children. Children are scored in the areas of communication, gross motor skills, fine motor skills, problem solving, and personal/social skills. The child's parent/guardian answers whether their child already does an activity (yes=10), sometimes does it (sometimes=5), or does not yet do it (not yet=0). The answers are then used to score each category. Each category is then broken down into whether the child falls above the cutoff (child development is on schedule), close to the cutoff (child development is slightly delayed and requires monitoring/intervention), or below the cutoff (delayed development and further assessment required). | ASQ-3 assessments were used for babies who were unable to have Bayley assessment performed due to COVID-19 research restrictions. The babies who had the Bayley did not have the ASQ. | Posted | Count of Participants | Participants | 12 months of age |
|
|
|
| Primary | Ages and Stages Questionnaire Third Edition (ASQ-3) | The ASQ-3 is a developmental screening tool to assess developmental progress in children. Children are scored in the areas of communication, gross motor skills, fine motor skills, problem solving, and personal/social skills. The child's parent/guardian answers whether their child already does an activity (yes=10), sometimes does it (sometimes=5), or does not yet do it (not yet=0). The answers are then used to score each category. Each category is then broken down into whether the child falls above the cutoff (child development is on schedule), close to the cutoff (child development is slightly delayed and requires monitoring/intervention), or below the cutoff (delayed development and further assessment required). | The ASQ-3 at 24 months was used for babies who were unable to have the Bayley assessment due to COVID-19 research restrictions. The babies who had the Bayley did not have the ASQ performed. | Posted | Count of Participants | Participants | 24 months |
|
|
|
| Primary | Childhood Behavior Checklist (CBCL) T-Scores | The CBCL/1.5-5 is validated for children ages 1.5 to 5 years old. It obtains caregivers' ratings of 113 behavior items. Scores are broken down into internalizing problems (scores range 29-100, normal is below 60), externalizing problems (scores range from 28-100, normal is below 60), and total problems (range is 28-100, normal is below 60). Items are scored on the following syndrome scales: Emotionally Reactive, Anxious/Depressed, Somatic Complaints, Withdrawn, Attention Problems, Aggressive Behavior, and Sleep Problems. Items are also scored on the following DSM-oriented scales: Affective Problems, Anxiety Problems, Pervasive Developmental Problems, Attention Deficit/Hyperactivity Problems, Stress Problems, Autism Spectrum Problems, and Oppositional Defiant Problems. The CBCL consists of 113 items, scored on a three-point Likert scale (0=absent, 1= occurs sometimes, 2=occurs often) | Only children in the treated cohorts had the CBCL. Participants who were considered lost to follow up did not have the CBCL. | Posted | Mean | Standard Deviation | score on a scale | Once post discharge (between 18 months up to 24 months of age) |
|
|
|
| Secondary | Duration of Treatment | Total number days of treatment | Posted | Mean | 95% Confidence Interval | days | 60 days |
|
|
|
| Secondary | Childhood Behavior Checklist 1.5-5 T-Scores | On the CBCL 1.5-5, T-scores, with a mean of 50 and a standard deviation of 10, are used to interpret results, with scores of 65 or higher indicating a clinical range, and scores between 60 and 64 suggesting a borderline clinical range. | Participants who were lost to follow up did not have the CBCL. | Posted | Count of Participants | Participants | Once post discharge (between 18 months up to 24 months of age) |
|
|
|
| 1 |
| 60 |
| 9 |
| 60 |
| 52 |
| 60 |
| EG001 | Morphine | Babies randomized to morphine will receive 0.06 mg/kg/dose (with a dosing interval of 3 or 4 hours). Morphine: Starting dose is 0.06 mg/kg/dose (every 3 or 4 hours), increases by 25% of initial dose every 12-24 hrs. Decrease by 10% of max dose every 24 hrs. | 0 | 60 | 15 | 60 | 24 | 60 |
|
| Skin lesions | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Hyperthermia | General disorders | Systematic Assessment |
|
| Respiratory Distress | Reproductive system and breast disorders | Systematic Assessment |
|
| Increased Heart Rate | Cardiac disorders | Systematic Assessment |
|
| Hematochezia | Gastrointestinal disorders | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | Systematic Assessment |
|
| Seizure | Nervous system disorders | Systematic Assessment |
|
| Respiratory Syncytial Virus | Infections and infestations | Systematic Assessment |
|
| Hypothermia | General disorders | Systematic Assessment |
|
| Dehydration | Gastrointestinal disorders | Systematic Assessment |
|
| Poor feeding | General disorders | Systematic Assessment |
|
| Pyloric stenosis | Gastrointestinal disorders | Systematic Assessment |
|
| Undescended testicle | Renal and urinary disorders | Systematic Assessment |
|
| Persistent ear infections | Ear and labyrinth disorders | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Adjunct medication added | Investigations | Systematic Assessment |
|
| Phenobarbitol added | Investigations | Systematic Assessment |
|
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| D006571 |
| Heterocyclic Compounds |
| D009022 | Morphine Derivatives |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| Motor |
|
| Motor |
|
| Motor |
|
| Below cutoffs |
|
| Gross motor |
|
| Fine motor |
|
| Problem solving |
|
| Personal/social |
|
| Below cutoffs |
|
| Gross motor |
|
| Fine motor |
|
| Problem solving |
|
| Personal/social |
|
| Total Problems |
|
| Externalizing Problems Borderline T-Scores |
|
| Externalizing Problems Clinical Range T-Scores |
|
| Total Problems Borderline T-Scores |
|
| Total Problems Clinical Range T-Scores |
|