A Phase 3 interventional study of Doxapram and Placebo in Apnea of Prematurity and Respiratory Insufficiency, sponsored by Erasmus Medical Center. Recruiting at 24 sites in 3 countries. Open to participants aged 23 Weeks to 29 Weeks. Per ClinicalTrials.gov, last updated 2024-04-04.
Sponsored by Erasmus Medical Center · Phase 3, Interventional, and Treatment
Preterm infants often suffer from apnea of prematurity (AOP; a cessation of breathing) due to immaturity of the respiratory system. AOP can lead to oxygen shortage and a low heart rate which might harm the development of the newborn, especially the central nervous system. In order to prevent oxygen shortage, infants are treated with non-invasive respiratory support and caffeine. Despite these treatments, many preterm newborns still suffer from AOP and need invasive mechanical ventilation. Although this will result in complete resolution of AOP, invasive mechanical ventilation has the disadvantage of being a major risk of chronic lung disease and impaired neurodevelopmental outcome. Restrictive invasive ventilation is therefore advocated nowadays in preterm infants. Doxapram is a respiratory stimulant that has been administered off-label to treat AOP. Doxapram, as add-on treatment, seems to be effective in treating AOP and to prevent invasive mechanical ventilation. It is unclear if a preterm infant benefit from doxapram treatment on the longer term. This study compares doxapram to placebo and hypothesizes that doxapram will protect preterm infants from both invasive ventilation (and related lung disease) and AOP related oxygen shortage (and related impaired brain development).
The main objective of the trial is to investigate if doxapram is safe and effective in reducing the composite outcome of death and neurodevelopmental impairment/severe disability at 2 years corrected age as compared to placebo. This multicenter double blinded randomized placebo-controlled superiority trial will be conducted in multiple neonatal intensive care units in the Netherlands and Belgium, including 8 years follow-up. After written informed-consent the patients will be randomized into the doxapram treatment group or the placebo treatment group. Randomization will be stratified based on center and gestational age \< or >= 26 weeks.
The participating departments include Dutch and Belgian Neonatal Intensive care units. The units include both academic and non-academic level III and IV units that are specialized in the care for critically ill and preterm born infants. Postnatal ages of patients at doxapram start vary from directly after birth up to months for the most-preterm born infants.
Blinded continuous doxapram or placebo (glucose 5%) will be infused as long as needed. Therapy is down titrated or stopped based on the patients' condition. If endotracheal intubation is needed study drug is stopped. After extubation study drug may be restarted. Switch to gastro-enteral administration is allowed if no iv-access is needed for other reasons. Next to study drug infusion, there will be no other study-related interventions. All outcome variables are already collected as standard of care. In a subset of patients doxapram plasma levels will be determined to validate the doxapram pharmacokinetic (PK) model. Blood will only be collected during routine blood sampling, with a maximum amount of 0.6 ml. Economic and cost-effectiveness evaluation will be performed. The national protocol for preterm birth advices follow-up at 2, 5.5 and 8 years respectively, as in the current study. Additional questionnaires will be used to collect data on the quality of life of patients and their parents.
1,650 studies on the registry are indexed under Respiratory Insufficiency; 296 are open to participants now.
This study's planned enrollment of 396 is above the median of 55 across 1,043 interventional studies indexed under Respiratory Insufficiency.
Browse Respiratory Insufficiency studies →Erasmus Medical Center is the lead sponsor of 466 studies on the registry; 179 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Blinded doxapram (2mg/ml, in glucose 5%) loading dose of 2.0 to 2.5 mg/kg administered in 5 to 10 minutes, followed by a continuous infusion of 0.5 - 1.0 mg/kg/hr ('www.kinderformularium.nl') as long as needed. Therapy is down titrated or stopped based on the patients' respiratory condition. If endotracheal intubation is needed study drug is stopped. After extubation study drug may be restarted. Switch to gastro-enteral administration is allowed if no iv-access is needed for other reasons.
Drug: Doxapram
Placebo (glucose 5%) will also be administered with a loading dose and continuous infusion (in equal amounts of fluid as in experimental arm) by intravenous or gastro-intestinal infusion. The treatment protocol will be equal to the protocol in the doxapram arm.
Drug: Placebo
Loading dose and continuous doxapram infusion.
Also known as: Dopram
Loading dose and continuous placebo infusion.
Also known as: Placebo (for Doxapram)
Death or severe disability
Disability will be defined as cognitive delay, cerebral palsy, severe hearing loss, or bilateral blindness. Cognitive delay will be defined as a Mental Development Index score of less than 85 on the Bayley Scales of Infant and Toddler Development, Bayley Score of Infant Development (BSID) III scores. Cerebral palsy will be diagnosed if the child had a non-progressive motor impairment characterized by abnormal muscle tone and decreased range or control of movements. The level of gross motor function will be determined with the use of the Gross Motor Function Classification System. Audiometry will be performed to determine the presence or absence of hearing loss. Blindness will be defined as a corrected visual acuity less than 20/200
Time frame: 2 years corrected age
Broncho pulmonary dysplasia
Diagnosed according to the National Institute of Child Health and Human Development (NICHD) criteria
Time frame: 36 weeks post menstrual age
Death
Death at 36 weeks post menstrual age and hospital mortality
Time frame: until 36 weeks post menstrual age and until hospital discharge
Admission period
Length of stay at the intensive care, length of stay in hospital
Time frame: through study completion and until discharge home, average 3 months
Endotracheal intubations
Incidence of endotracheal intubations
Time frame: Day 3, 7, 14, and 21 after start of study medication
Oxygenation days and complications
Number of days on invasive ventilation, number of days on ventilatory support (non-invasive ventilation, CPAP, humidified high flow, low flow), number of days with supplemental oxygen, respiratory complications (airleak, pneumonia, etc), use of (rescue) corticosteroids for respiratory reasons.
Time frame: During first hospital admittance and through study completion, average of 3 months
Gastro-intestinal outcome measures
solitary intestinal perforation, necrotizing enterocolitis \> stage 2 according to Bell, feeding problems with need for parental feeding (days with parental feeding after inclusion), body weight (gain, length), head circumference
Time frame: During first hospital admittance and until 36 weeks post menstrual age
Neurological outcome measures
Intraventricular hemorhage(IVH) (all grades, grade III-IV, venous infarction), clinical seizures, periventricular leucomalacia (PVL) \> gr 1)
Time frame: During first hospital admittance or at term equivalent age (37-42 weeks postmenstrual age), average 3 months
Complications during neonatal period
Incidence of late onset sepsis (culture proven or clinical suspected) and meningitis after inclusion, need for inotropes/circulatory support
Time frame: During first hospital admittance or at term equivalent age (37-42 weeks postmenstrual age), average 3 months
Retinopathy of prematurity
Grade of retinopathy (including plus disease and need for therapy)
Time frame: During first hospital admittance or at term equivalent age (37-42 weeks postmenstrual age), average 3 months
Hearing
Hearing test
Time frame: At term equivalent age, 37-42 weeks postmenstrual age, average 3 months
Additional long term outcomes
Readmissions since first discharge home, weight/length/head circumference, behavioral problems (Child Behavior Checklist)
Time frame: 2 years corrected age
Parent reported outcome
Parent reported outcome with the PARCA-R (Parent Report of Children's Abilities-Revised) questionnaire (expected mean standardised scores 100 (SD 15), higher score is better outcome)
Time frame: 2 years corrected age
Plan to share: Yes — Yes
Supporting information: Study protocol, Sap, Icf, Csr, Analytic code
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Erasmus Medical Center