Doxapram Therapy in Preterm Infants (DOXA Trial)

Last updated: April 3, 2024
Sponsor: Erasmus Medical Center
Overall Status: Active - Recruiting

Phase

3

Condition

Lung Injury

Respiratory Failure

Treatment

Placebo

Doxapram

Clinical Study ID

NCT04430790
NL72125.078.19
2019-003666-41
80-84800-9843009
  • Ages 23-29
  • All Genders

Study Summary

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).

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Admitted to the neonatal intensvie care unit (NICU) of one of the participatingcentres
  • Written informed consent of both parents or legal representatives
  • Gestational age at birth < 29 weeks
  • Caffeine therapy, adequately dosed (see also under co-medication)
  • Optimal Non-invasively supported with nasal Continuous Positive Airway Pressure (CPAP)or ventilation ((S)NIPPV, NIV-NAVA, BIPAP/Duopap, SIPAP)
  • Apnea that require a medical intervention as judged by the attending physician

Exclusion

Exclusion Criteria:

  • Previous use of open label doxapram
  • Use of theophylline (to replace doxapram)
  • Chromosomal defects (e.g. trisomy 13, 18, or 21)
  • Major congenital malformations that: compromise lung function (e.g. surfactant proteindeficiencies, congenital diaphragmatic hernia); result in chronic ventilation (e.g.Pierre Robin sequence); increase the risk of death or adverse neurodevelopmentaloutcome (congenital cerebral malformations, chromosomal abnormalities);
  • Palliative care or treatment limitations because of high risk of impaired outcome.

Study Design

Total Participants: 396
Treatment Group(s): 2
Primary Treatment: Placebo
Phase: 3
Study Start date:
June 15, 2020
Estimated Completion Date:
May 01, 2034

Study Description

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.

Connect with a study center

  • St Luc Louvain

    Brussels, Avenaue Hippocrate 10 1200
    Belgium

    Active - Recruiting

  • Delta Hospital Brussels

    Brussels, Brussels Hoofdstedelijk Gewest 1160
    Belgium

    Active - Recruiting

  • University Hospital Brussels

    Jette, Brussels Hoofdstedelijk Gewest 1090
    Belgium

    Active - Recruiting

  • Grand Hospital de Charleroi

    Charleroi, Henegouwen
    Belgium

    Active - Recruiting

  • Clinique Saint-Vincent Liege

    Liège, Liege 4000
    Belgium

    Suspended

  • Academisch Ziekenhuis Sint-Jan

    Brugge, West-Vlaanderen 8000
    Belgium

    Active - Recruiting

  • Sint Augustinus Hospital Antwerp

    Antwerp, 2610
    Belgium

    Active - Recruiting

  • University Hospital Antwerp

    Antwerp, 2650
    Belgium

    Active - Recruiting

  • Chirec-Delta Hospital

    Brussels, 1160
    Belgium

    Active - Recruiting

  • University Hospitals Leuven

    Leuven,
    Belgium

    Active - Recruiting

  • Alberta Health Services Foothills Hospital

    Calgary, Alberta T2N 2T9
    Canada

    Site Not Available

  • Foothills Medical Centre

    Calgary, Alberta T2N 2T9
    Canada

    Site Not Available

  • Royal Alexandra Hospital

    Edmonton, Alberta T5H 3V9
    Canada

    Site Not Available

  • McMaster Children's Hospital

    Hamilton, Ontario L8N3Z5
    Canada

    Site Not Available

  • Montreal Children's Hospital

    Montreal, Quebec QC H4A 3J1
    Canada

    Site Not Available

  • Centre Mère-Enfent Soleil

    Quebec City, Quebec G1V 4G2
    Canada

    Site Not Available

  • Radboudumc Amalia Children's Hospital Nijmegen

    Nijmegen, Gelderland 6525 GA
    Netherlands

    Active - Recruiting

  • Maastricht University Medical Center

    Maastricht, Limburg 6229 HX
    Netherlands

    Active - Recruiting

  • Maxima Medical Center Veldhoven

    Veldhoven, Noord-Brabant 5504 DB
    Netherlands

    Active - Recruiting

  • Amsterdam University Medical Center

    Amsterdam, Noord-Holland 1105 AZ
    Netherlands

    Active - Recruiting

  • Isala Clinics Zwolle

    Zwolle, Overijssel 8025 AB
    Netherlands

    Active - Recruiting

  • Leiden University Medical Center

    Leiden, Zuid-Holland 2333 ZA
    Netherlands

    Active - Recruiting

  • Erasmus Medical Center - Sophia Children's Hospital

    Rotterdam, Zuid-Holland 3015 GD
    Netherlands

    Active - Recruiting

  • University Medical Center Groningen

    Groningen, 9713 GZ
    Netherlands

    Active - Recruiting

  • UMC Utrecht - Wilhelmina Kinderziekenhuis

    Utrecht, 3584 EA
    Netherlands

    Active - Recruiting

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