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

Prematurity Clinical Trial

— NOSE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05878925
• Other study ID #: NOSE-Trial
• Status: Recruiting
• Phase: N/A
• Start date: June 14, 2023
• Est. completion date: May 1, 2025

Study information

• Verified date: July 2023
• Source: University of Zurich
• Contact: Janine Thomann, MD
• Phone: 0041432538774
• Email: janine.thomann[@]usz.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: May 1, 2025
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 72 Hours and older

Eligibility

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

Related Conditions & MeSH terms

• Apnea of Prematurity
• Infant, Premature, Diseases
• Premature Birth
• Prematurity

Intervention

Other:
• Aroma
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
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.

Locations

Country	Name	City	State
Switzerland	Department of Neonatology, Newborn Research, University Hospital and University of Zurich,	Zürich

Sponsors (2)

Lead Sponsor	Collaborator
University of Zurich	Bangerter-Rhyner Foundation

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Prespecified subgroup analyses of the primary outcome will be performed according to the type of aroma (vanilla or strawberry) that was administered.	A prespecified subgroup analysis for the primary outcome will be performed between infants receiving vanilla and strawberry aroma.	12-hour recording periods for each intervention
Primary	Paired difference in the combined number of desaturations and bradycardia	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.	12-hour recording periods for each intervention
Secondary	Paired difference in fraction of inspired oxygen (FiO2)	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	12-hour recording periods for each intervention
Secondary	Paired difference in mean peripheral oxygen saturation	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.	12-hour recording periods for each intervention
Secondary	Paired difference in time spent with peripheral oxygen saturations <80%	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.	12-hour recording periods for each intervention
Secondary	Paired difference in time spent with heart rate <80 bpm	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.	12-hour recording periods for each intervention
Secondary	Paired difference in mean respiratory rate (as counted by nurses and manually) documented according to clinical routine) and heart rate	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.	12-hour recording periods for each intervention
Secondary	Paired difference in the apnea score documented by nurses	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.	12-hour recording periods for each intervention
Secondary	Paired difference in desaturations requiring stimulation or increase in FiO2	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.	12-hour recording periods for each intervention
Secondary	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)	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.	12-hour recording periods for each intervention