Pharmacokinetic and pharmacodynamic modelling of routinely used off label drugs in premature neonates

Pharmacokinetic and pharmacodynamic modelling of routinely used off label drugs in premature neonates - DINO study

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON44214

Enrollment

600

Registered

2014-05-21

Start date

2014-09-10

Completion date

Unknown

Last updated

2024-04-23

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

Conditions

Pijn en sedatie Prematurity

Interventions

None listed

Eligibility

Age

2 Years to 11 Years

Inclusion criteria

Inclusion criteria: * Gestational age

Exclusion criteria

Exclusion criteria: None

Design outcomes

Primary

Measure	Time frame
1) Pharmacokinetic endpoints are clearance en volume of distribution.	—

Secondary

Measure	Time frame
Pharmacodynamics of all drugs used will be explored in all included preterm neonates. Drug specific effects of drugs (e.g. pain scores for morphine, blood pressure for dopamine) as well as side effects and short term effects on morbidity and outcome will be analyzed. Additional pharmacodynamic endpoints for 8 of the 9 study drugs is the Drug target concentration for each drug that is related to the desired effect. Fluconazole will only be studied for the PK. The parameters to measure the effect of the drugs: a) Fentanyl and paracetamol, used as analgetics; clinical endpoint is pain relief, as routinely measured by the validated COMFORTneo scale and the NRS scale. b) Midazolam, phenobarbital and levetiracetam, used as anticonvulsive drugs; clinical endpoint is control of convulsions, measured by Cerebral Function Monitoring using amplitude-integrated EEG (aEEG). c) Midazolam and fentanyl, used as a sedative drug during endotracheal intubation; clinical endpoint is the intubation readiness score (IRS) and a qualitative intubation score and sedation score. d) Midazolam and fentanyl, used as a sedative drug during nursing care is measured by the COMFORTneo scale. e) Doxapram, used as treatment for neonatal apnea; clinical endpoint is control of neonatal apnea and endotracheal intubation in case of failure. The first endpoint can be measured by modern monitoring technology, in which central post-monitoring data stored after initiation of treatment will reveal the effect of doxapram on the reduction or elimination of apneas. f) Sildenafil, a treatment for PPHN; clinical endpoints are level of ventilatory support, oxygen need (repetitive oxygenation index analyses) and BPD development. g) Ibuprofen, a treatment for PDA; clinical endpoint is closure of the ductus arteriosus. Echocardiographic imaging allows the measurement of the diameter of the ductus and to calculate the LA/AO ratio (left atrial to aortic root ratio). Inter- and intra-patient	—

Measure

Time frame

Pharmacodynamics of all drugs used will be explored in all included preterm neonates. Drug specific effects of drugs (e.g. pain scores for morphine, blood pressure for dopamine) as well as side effects and short term effects on morbidity and outcome will be analyzed. Additional pharmacodynamic endpoints for 8 of the 9 study drugs is the Drug target concentration for each drug that is related to the desired effect. Fluconazole will only be studied for the PK. The parameters to measure the effect of the drugs: a) Fentanyl and paracetamol, used as analgetics; clinical endpoint is pain relief, as routinely measured by the validated COMFORTneo scale and the NRS scale. b) Midazolam, phenobarbital and levetiracetam, used as anticonvulsive drugs; clinical endpoint is control of convulsions, measured by Cerebral Function Monitoring using amplitude-integrated EEG (aEEG). c) Midazolam and fentanyl, used as a sedative drug during endotracheal intubation; clinical endpoint is the intubation readiness score (IRS) and a qualitative intubation score and sedation score. d) Midazolam and fentanyl, used as a sedative drug during nursing care is measured by the COMFORTneo scale. e) Doxapram, used as treatment for neonatal apnea; clinical endpoint is control of neonatal apnea and endotracheal intubation in case of failure. The first endpoint can be measured by modern monitoring technology, in which central post-monitoring data stored after initiation of treatment will reveal the effect of doxapram on the reduction or elimination of apneas. f) Sildenafil, a treatment for PPHN; clinical endpoints are level of ventilatory support, oxygen need (repetitive oxygenation index analyses) and BPD development. g) Ibuprofen, a treatment for PDA; clinical endpoint is closure of the ductus arteriosus. Echocardiographic imaging allows the measurement of the diameter of the ductus and to calculate the LA/AO ratio (left atrial to aortic root ratio). Inter- and intra-patient

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Countries

Netherlands

Outcome results