Trial document




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  DRKS00005387

Trial Description

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Title

Randomised crossover trial of different nasal support systems for the treatment of apnea of prematurity

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Trial Acronym

NASUS

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URL of the Trial

[---]*

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Brief Summary in Lay Language

About 80% of infants born before 32 weeks of pregnancy develop intermittent episodes involving pauses in breathing (apnea), slow heart rate (bradycardia) and decreases in oxygen levels (hypoxemia; together called apnea of prematurity or AoP). These are related to their yet immature control of breathing. To avoid the frequent decreases in oxygen saturation, ventilatory support is applied. In this context, a continuous positive airway pressure (CPAP) is delivered to facilitate respiration. Furthermore there is the possibility to apply additional air blasts in periodical intervals expanding the lungs as during a deep inhalation or to make the airflow oscillate.

In order to apply the airflow by nose, two different devices are available which differ in their design and functioning. Therefore, the effect on breathing varies likewise. Both devices are routinely used in many neonatal intensive care units, including ours, for the treatment of AoP. However, it is unclear which device and mode of breathing support reduces the number of hypoxias and bradycardias most effectively. This question is now to be investigated at our hospital. During the intervention phase three different modes of CPAP (device 1 without air blasts, device 2 with air blasts, device 2 without air blasts but with oscillations of the air column) are applied for a period of 8 hours each, and the number and severity of decreases in oxygen saturation and heart rate are recorded and analysed. For determining daily fluctuations in these decreases, the last CPAP mode is to be continued for an observation period lasting an additional 24 hours. To measure the decreases in oxygen saturation and heart rate, an oxygen saturation sensor is attached to the infant’s foot as used in routine medical care.

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Brief Summary in Scientific Language

Apnea of prematurity (AOP) is a common problem in preterm infants as 80% of all infants with a gestational age < 32 weeks show clinically relevant apneas and desaturations. Therapeutic approaches involve treatment with respiratory stimulants on the one hand and ventilatory support via nasal support systems on the other. Due to the fact that the exclusive treatment with methylxanthines (caffeine and theophylline) often lacks the required effectiveness, additional measures such as the application of continuous positive airway pressure (CPAP) or re-intubation have to be conducted.

Nasal CPAP is an established method for the treatment of AOP in daily clinical practice. The theoretical background is based on the assumption that it increases functional residual capacity and reduces airway resistance. In addition it is assumed that the frequency of apneas is reduced by influencing the Hering-Breuer inflation reflex and inhibitory intercostal reflex pathways. In most cases the positive airway pressure is generated by a conventional ventilator, yet there are more recent methods such as the Infant Flow System in which CPAP is generated by the Venturi effect. The combination of CPAP and nasal ventilation represents another important development of which nasal intermittent mandatory ventilation (N-IMV) and nasal high frequency oscillatory ventilation (N-HFOV) are the main representatives. The pros and cons as well as the efficacy of the ventilatory support systems listed here have not been clarified adaequately and it remains unclear which mode is most effective. In a preliminary study we were able to show a positive effect on AOP applying the Infant Flow CPAP system in comparison with three other nasal ventilatory support modes.

The actual study investigates the efficacy of two new nasal CPAP/ventilation modes on the rate of intermittent hypoxia and bradycardia in preterm infants. A comparison between the most effective system of the preliminary study and two additional nasal respiratory support systems (N-IMV, N-HFOV), being established in the routine clinical use for many years, is to be made. The primary outcome is the cumulative event rate of bradycardias (< 80 beats per minute) and desaturations (< 80% arterial oxygen saturation measured by pulse oximetry). In contrast to the Infant Flow CPAP system, it is expected that the rate of intermittent hypoxia and bradycardia decreases using the SIMV support. Secondary endpoints are mean FiO2, mean tcPCO2 and change in abdominal girth during each 8-hour interval the treatments are applied. The duration of the intervention phase per test person amounts 24 hours: each preterm infant is treated for 8 hours with each of the three systems, in doing so the sequence of treatment variations varies according to a randomisation scheme (contained in sealed opaque envilopes). For determining potential effects of the circadian rhythm and carryover effects of the different treatment variations, the last CPAP mode is continued for an observation phase of another 24 hours.

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Organizational Data

  •   DRKS00005387
  •   2013/11/12
  •   [---]*
  •   yes
  •   Approved
  •   705/2011BO1, Ethik-Kommission an der Medizinischen Fakultät der Eberhard-Karls-Universität und am Universitätsklinikum Tübingen
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Secondary IDs

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Health Condition or Problem studied

  •   P28.4 -  Other apnoea of newborn
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Interventions/Observational Groups

  •   Nasal CPAP via variable flow device (Infant Flow; Electro Medical Equipment, Brighton, UK) (PEEP 6 cm H2O)
  •   Nasal CPAP using a conventional respirator (Stephanie; Stephan, Gackenbach, Germany) with application of respiratory support by Hudson prongs and additional background support, synchronisation via Graseby Respiration Sensor placed on the abdomen (SIMV f=20/min, P insp.: 15 cm H2O, PEEP: 6 cm H2O)
  •   Nasal CPAP using a conventional respirator (Stephanie; Stephan, Gackenbach, Germany) with application of respiratory support by Hudson prongs and additional background support via high frequency ventilation (variable amplitude, P osz.: 15 cm H2O, MAP: 6 cm H2O)
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   assessor
  •   Active control
  •   Treatment
  •   Crossover
  •   N/A
  •   N/A
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Primary Outcome

Combined rate of intermittent hypoxia (SpO2 <80%) and bradycardia (pulse rate <80/min.) per hour. The recording of aterial oxygen saturation is carried out using a Vitaguard 300 (Getemed, Teltow, Germany) monitor for a period of 48 hours (each intervention for 8 hours, then the last one for another 24 hours).

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Secondary Outcome

Mean FiO2, mean tcPCO2 and change of abdominal girth during the particular 8-hour interval (documentation through nursing staff).

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2013/12/16
  •   37
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   no minimum age
  •   38   Weeks of pregnancy
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Additional Inclusion Criteria

Gestational age at birth ≤ 34 0/7 weeks; age at study performance ≤ 38 0/7 weeks; persistent apneas despite administration of caffeine; apnea-score ≥ 6 (a score used routinely at our neonatal intensive care unit to monitor the frequency and severity of apneas); parental approval and written informed parental consent

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Exclusion Criteria

Congenital severe dysplasia (e.g. congenital heart defect, chromosome abnormality); symptomatic apnea due to sepsis, epileptic seizure, hypoglycemia or intracerebral haemorrhage; neuromuscular, muscular or skeletal disease; necessity of changing the dosis of caffeine or doxapram; necessity of intubation and mechanical ventilation

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Addresses

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Sources of Monetary or Material Support

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    • Universitätsklinik für Kinder- und Jugendmedizin, Abt. IV Neonatologie
    • Mr.  Prof. Dr. med.  Christian F.  Poets 
    • Calwerstr. 7
    • 72076  Tübingen
    • Germany
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Status

  •   Recruiting ongoing
  •   [---]*
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.