Oxygen Therapy in Cystic Fibrosis
Oxygen Therapy in Cystic Fibrosis
This is an open, multicenter, prospective, randomised and cross over study, comparing in
 patients with cystic fibrosis aged > 6 years, 2 periods of 6 weeks of oxygen therapy or room
 air, separated by a wash out period of 2 to 6 weeks.
Rationale Oxygen therapy may be proposed to patients with cystic fibrosis (CF) with nocturnal
 hypoxemia but the indication and benefits of oxygen therapy have not been validated in CF.

 Aim of the study and main objective The aim of the study is to evaluate the improvement in
 nocturnal hypoxemia by the measurement of nocturnal pulse oximetry (SpO2) after 6 weeks of
 nocturnal oxygen therapy in stable patients with CF.

 An improvement is defined by a nocturnal SpO2 > 90% during the whole night.

 Objectives and secondary aims

 -  Comparison of subjective sleep quality during oxygen therapy and room air after a period
 of 6 weeks by means of 4 validated sleep questionnaires

 -  Comparison of quality of life during oxygen therapy and room air after a period of 6
 weeks by means of a validated questionnaire for CF patients (CFQ).

 -  Detection of the appearance or increase in nocturnal hypercapnia during oxygen therapy
 and room air after a period of 6 weeks

 -  Comparison of a possible arterial pulmonary hypertension during oxygen therapy and room
 air after a period of 6 weeks by means of an echocardiography

 Study design This is an open, multicentre, prospective, randomised and cross over study,
 comparing in individual patient two periods of 6 weeks: one period with nocturnal oxygen
 therapy and one period in room air, separated by a wash out period of 2 to 6 weeks.

 Inclusion criteria

 -  Children ≥ 6 years and adults ≥ 18 years with CF in a stable state

 -  With a forced expiratory volume in one second (FEV1) ≤ 50% of predicted value

 -  Having a pulse oximetry (SpO2) in room air ≤ 90% for ≥ 10% of the night and/or a SpO2 ≤
 90% for ≥ 10 minutes during the night

 -  Any patient with prior noninvasive positive pressure ventilation (NPPV) but who has
 stopped NPPV at least 15 days before the start of the study.

 -  Written approval by the patient and by the parents in case of a pediatric patient

 -  Patient having the French social security coverage Non-inclusion criteria

 -  Patients with a respiratory exacerbation during the last 15 days

 -  Patients with NPPV or long term oxygen therapy prior to the start of the study and
 unable to stop this treatment

 -  Impossibility of a medical examination

 -  Pregnant patient or breastfeeding patient

 Study protocol The study is proposed to the patients during the V0 visit, corresponding to
 the screening monitoring showing a nocturnal SpO2 in room air ≤ 90% for ≥ 10% of the night
 and/or a SpO2 ≤ 90% for ≥ 10 minutes during the night. After a period of 2 to 30 days, the
 written approval is obtained during a routine visit.

 Thereafter, the patient will be randomised to receive either:

 1. nocturnal oxygen therapy with a stable flow to obtain a nocturnal SpO2 >90% (Oxygen
 period) while continuing his routine long term treatment

 2. his routine long term treatment without nocturnal oxygen therapy (Air period) During the
 Oxygen period, the oxygen flow will be at least 1.5 L/min. This flow may be increased up
 to 2L/min in case of the presence of nocturnal periods with a SpO2 ≤ 90%.

 The two periods Oxygen and Air will be separated by a wash out period of 2 to 6 weeks to rule
 out any long lasting effect of nocturnal oxygen therapy.

 At the end of the 2 periods of 6 weeks oxygen or air, the following investigations will be
 performed:

 -  A nocturnal evaluation of gas exchange by the Sentec™ monitor (which measures SpO2 and
 transcutaneous carbon dioxide (PCO2)) and objective sleep quality by means of actigraphy

 -  an evaluation of subjective sleep quality by means of 4 validates sleep questionnaires

 -  an evaluation of quality of life by a validated CF questionnaire (CFQ)

 -  spirometry with blood gases in room air

 -  an echocardiography

 Number of subjects Only 3 studies have evaluated the benefit of oxygen therapy on nocturnal
 gas exchange during one night and only one study has evaluated the benefit of oxygen therapy
 after a period of 26 months. This last study is limited by the small number of patients and
 the low compliance with oxygen therapy.

 No study has evaluated the effect of oxygen therapy during a 6 weeks period. This limits the
 calculation of the number of subjects.

 As the study is a cross over study, a number of 30 analysable patients is estimated to be
 sufficient for the evaluation of the primary outcome measure and the secondary outcomes.
 Because of the possibility of premature withdrawal, it is planned to include 50 patients.

 Total duration of the study: maximum 22.5 months

 Inclusion period: 18 months

 Duration of participation for one patient: maximum 4.5 months

 Statistical analysis and final report: 3 months

 Number of participating centres: 8

 Estimation of the mean number of patients included per centre: 3 patients / 3 months / centre

 Expected results The results of the present study should help to define the criteria to start
 long term oxygen therapy and to assess the potential benefits of this treatment in stable
 patients with CF.
Inclusion Criteria:

 -  Children ≥ 6 years and adults ≥ 18 years with CF in a stable state

 -  With a forced expiratory volume in one second (FEV1) ≤ 50% of predicted value

 -  Having a pulse oximetry (SpO2) in room air ≤ 90% for ≥ 10% of the night and/or a SpO2
 ≤ 90% for ≥ 10 minutes during the night

 -  Any patient with prior noninvasive positive pressure ventilation (NPPV) but who has
 stopped NPPV at least 15 days before the start of the study.

 -  Written approval by the patient and by the parents in case of a pediatric patient

 -  Patient having the French social security coverage

 Exclusion Criteria:

 -  Patients with a respiratory exacerbation during the last 15 days

 -  Patients with NPPV or long term oxygen therapy prior to the start of the study and
 unable to stop this treatment

 -  Impossibility of a medical examination

 -  Pregnant patient or breastfeeding patient