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Completed

NCT Number: NCT05878925

Nasal Olfactory Stimulation and Its Effect on Respiratory Drive in Preterm Infants

This trial analyzes the effect of an olfactory stimulation with vanilla or strawberry aroma compared to placebo on desaturations and bradycardia in preterm infants with apnea of prematurity. Infants on continuous positive airway pressure (CPAP) support will be included and the aroma will be applied to the inner surface of the CPAP mask using designated scent pens. The trial uses a cross-over design. Infants are randomised to begin the study with either aroma or placebo which will be applied into the breathing mask every 3 to 4 hours during 12 hours for each of the two intervention periods. Identically looking pens with either aroma or placebo are used and patients, parents, medical staff and the study team are blinded to this allocation. Infants are monitored with an oximetry sensor to measure peripheral oxygen saturation (SpO2) and pulse rate.

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Key information

Conditions

Apnea of Prematurity Apnea Congenital, Hereditary, and Neonatal Diseases and Abnormalities Female Urogenital Diseases and Pregnancy Complications Infant, Newborn, Diseases Infant, Premature, Diseases Obstetric Labor Complications Obstetric Labor, Premature Pathological Conditions, Signs and Symptoms Pregnancy Complications Premature Birth Prematurity Respiration Disorders Respiratory Tract Diseases Signs and Symptoms Signs and Symptoms, Respiratory Urogenital Diseases

Age range

72 hour and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Department of Neonatology, Newborn Research, University Hospital and University of Zurich,

Zurich, 8091, Switzerland

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Gestational age at birth: 23 0/7 to 31 6/7 weeks
  • Postnatal age: >72 hours old
  • Respiratory support: nCPAP
  • Treatment with caffeine citrate for apnea of prematurity
  • Written informed consent by one of the patient's parents

Exclusion criteria

  • Olfactory impairment such as choanal atresia
  • Intraparenchymal intracranial hemorrhage or intraventricular hemorrhage with ventricular dilation
  • Culture-proven sepsis during the study period or any acute clinical deterioration requiring an intervention such as intubation or a new start of antibiotic treatment.
  • Severe congenital malformation adversely affecting life expectancy

Treatment and study plan

Aroma

Other

The study intervention is an olfactory stimulation with vanilla or strawberry aroma. The aroma will be applied to the inner surface of the nCPAP mask of preterm infants using designated scent pens every 3-4 hours over a period of 12 hours. The two aromas will be applied in blocks of 5 consecutive infants (5 infants vanilla, 5 infants strawberry, and so forth).

Placebo

Other

During the control intervention, identically looking placebo pens will be used to apply a colored carrier solution (without aroma) to the inner surface of the nCPAP mask of preterm infants in the same manner.

Primary outcomes

  1. Paired difference in the combined number of desaturations and bradycardia

    Time frame: 12-hour recording periods for each intervention

    A desaturation is defined as a fall in the SpO2 to <80% for more than 10 seconds, a bradycardia is defined as a fall in heart rate <80 bpm for more than 10 seconds. Desaturation episodes and bradycardia separated by a time interval of five seconds or less will be counted as a single event. A desaturation episode as part of a bradycardia (or vice versa) will be counted as a two events. Peripheral oxygen saturation and heart rate will be monitored with an oximeter sensor placed around the infants' wrist or ankle and connected to the oximeter in 2 seconds averaging mode and maximum sensitivity.

Secondary outcomes

  1. Paired difference in fraction of inspired oxygen (FiO2)

    Time frame: 12-hour recording periods for each intervention

    Paired difference in oxygen requirement between the two intervention periods. The FiO2 will be measured by the infant ventilator and documented in the patient data management system

  2. Paired difference in mean peripheral oxygen saturation

    Time frame: 12-hour recording periods for each intervention

    Paired difference in oxygen saturation between the two intervention periods. Peripheral oxygen saturation and heart rate will be monitored with an oximeter sensor placed around the infants' wrist or ankle and connected to the oximeter in 2 seconds averaging mode and maximum sensitivity.

  3. Paired difference in time spent with peripheral oxygen saturations <80%

    Time frame: 12-hour recording periods for each intervention

    Paired difference in total time spent with an oxygen saturation <80% between intervention periods. Peripheral oxygen saturation and heart rate will be monitored with an oximeter sensor placed around the infants' wrist or ankle and connected to the oximeter in 2 seconds averaging mode and maximum sensitivity.

  4. Paired difference in time spent with heart rate <80 bpm

    Time frame: 12-hour recording periods for each intervention

    Paired difference in total time spent with a heart rate <80 beats per minute between intervention periods. Peripheral oxygen saturation and heart rate will be monitored with an oximeter sensor placed around the infants' wrist or ankle and connected to the oximeter in 2 seconds averaging mode and maximum sensitivity.

  5. Paired difference in mean respiratory rate (as counted by nurses and manually) documented according to clinical routine) and heart rate

    Time frame: 12-hour recording periods for each intervention

    Paired difference in mean respiratory rate between intervention periods. Respiratory rate will be counted and documented by nurses every 4 to 8 hours according to clinical standard and documented in the patient data management system.

  6. Paired difference in the apnea score documented by nurses

    Time frame: 12-hour recording periods for each intervention

    Paired difference in the apnea score (objective scoring system for the number and severity of apneas during a dedicated time frame) between intervention periods. Definition of the apnea score: Cumulative number of bradycardia <80 bpm and desaturations <80% during sleep and unimpaired wakefulness. Score 1 for event without need for intervention, score 2 for event requiring tactile stimulation, score 3 for event requiring increase of FiO2, score 8 for event requiring mask ventilation.

  7. Paired difference in desaturations requiring stimulation or increase in FiO2

    Time frame: 12-hour recording periods for each intervention

    Paired difference in the total number of desaturations requiring manual stimulation or an increase in supplemental oxygen between intervention periods. Manual stimulation will be documented by nurses in the patient data management system.

  8. Paired difference in tolerance of enteral nutrition as assessed by gastric residuals (the amount of stomach liquid detected prior to the next meal, in mL)

    Time frame: 12-hour recording periods for each intervention

    Paired difference in amount of gastric residuals (mL) between intervention periods. Before each feed, nurses routinely aspirate orogastric tubes to check for the liquid volume and document the amount in mL in the patient data management system.

Other outcomes

  1. Prespecified subgroup analyses of the primary outcome will be performed according to the type of aroma (vanilla or strawberry) that was administered.

    Time frame: 12-hour recording periods for each intervention

    A prespecified subgroup analysis for the primary outcome will be performed between infants receiving vanilla and strawberry aroma.

Sponsors and collaborators

Lead sponsor

University of Zurich

Other

Collaborators

  • Bangerter-Rhyner Foundation

Registry information

Official study title

Nasal Olfactory Stimulation and Its Effect on Respiratory Drive in Preterm Infants - A Randomized Cross-over Study

Acronym: NOSE

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
May 30, 2023
Registry last updated
Apr 4, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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