The Effect of Oxygen Therapy on 6MWD in PAH and CTEPH Patients With Hypoxemia
The Effect of Oxygen Therapy on 6MWD in PAH and CTEPH Patients With Hypoxemia
Treatment of O2 naïve patients with PAH will be included in this investigator-initiated trial
 (IIT) to assess efficacy and safety of oxygen substitution. Nocturnal oxygen substitution
 improved the 6MWD compared to placebo in one clinical trial in PAH patients. Due to the
 positive results in the treatment of patients with PAH, the initiation of this
 proof-of-concept study is justified.
Most patients with PAH, except those with congenital heart defects and pulmonary-to-systemic
 shunts, have minor degrees of hypoxemia at rest and during the night.Current recommendations
 including the pneumological guidelines for LTOT are based on evidence in patients with
 chronic obstructive pulmonary disease, as data for patients with PH are lacking: When O2
 partial pressure is repeatedly <8 kPa (<60 mmHg, alternatively, 90% of O2 saturation),
 patients are advised to use O2 to achieve a saturation of >8 kPa. The use of ambulatory O2
 can be considered when there is evidence of a symptomatic response or correction of
 exercise-induced desaturation.

 There are only few studies investigating the effect of oxygen supply in pulmonary
 hypertension, most of which merely investigate acute effects of O2 administration. Short-term
 oxygen administration has been shown to reduce mean pulmonary arterial pressure, pulmonary
 vascular resistance and to increase cardiac output in PAH patients. In one study, oxygen
 supply also reversed the progression of PH in patients with chronic obstructive pulmonary
 disease (COPD). One recent randomized-controlled trial indicates that O2 given during
 cardiopulmonary exercise significantly improves maximal work rate and endurance. Furthermore,
 nocturnal oxygen supply for one week significantly improved 6-minute walking distance in
 patients with PH, sleep-associated breathing difficulties, exercise performance during the
 day as well as cardiac repolarisation. Patients with Eisenmenger's syndrome gain little
 benefit from nocturnal O2 therapy.

 Whether these positive effects of O2 supplementation during exercise would translate into
 long-term improvements of exercise capacity, quality of life, hemodynamics and disease
 progression is not known to date. Up to now, there are no randomised studies suggesting that
 long-term O2 therapy is indicated or when it should be initiated.
Inclusion Criteria Patients in both groups (n = 20; n=10 each group) with precapillary PH,
 WHO class I -IV (mPAP ≥ 25 mm Hg, pulmonary arterial occlusion pressure ≤15 mm Hg), who are
 stable on optimized pharmacological treatment for at least six weeks and who do not suffer
 from other cardio-pulmonary disease will be recruited if arterial or capillary O2 partial
 pressure is (<60 mmHg; alternatively, 90% of O2 saturation) at rest and/or during physical
 activity (O2 partial pressure <60 mmHg pO2 90 % ).

 -  men and women 18 years of age or older

 -  patient is diagnosed with Pulmonary Arterial Hypertension (World Health Organization
 (WHO) Category Group 1 (by the WHO Clinical classification system)), including
 Idiopathic (IPAH), Heritable PAH (HPAH, Familial PAH), associated PAH (APAH) and
 CTEPH, with exceptions as noted in exclusion criteria

 -  patient is willing and able to provide written informed consent

 -  patient is willing and able to comply with the protocol, including required follow-up
 visits

 -  Patients experiencing oxygen desaturations ≤90% (or pO2 below 60 mmHg) at rest and/or
 oxygen desaturations ≤90% (or pO2 below 60 mmHg) during physical activity

 -  patient has a stable functional class of PAH with no changes of medication during the
 last two weeks before inclusion

 Exclusion Criteria

 -  Patient is a female who is pregnant, nursing, or of child bearing potential and is not
 on a reliable form of birth control

 -  patient with pulmonary venous hypertension

 -  significant functional limitation in lung function tests (FEV1 <60%,TLC <60%) and CT
 morphological signs of pulmonary disease

 -  significant left heart disease, requiring acute pharmacological or interventional
 treatment

 -  unstable conditions requiring pharmacological or other treatment, intensive care or
 relevant severe concomitant disease

 -  patient is enrolled, has participated within the last thirty days, or is planning to
 participate, in a concurrent drug and/or device study during the course of this
 clinical trial. Co-enrolment in concurrent trials is only allowed with documented
 pre-approval from the study manager that there is not a concern that co-enrolment
 could confound the results of this trial.

 -  patient has been initiated on a new oral or parenteral PAH therapy in the last two
 weekspatient with a cardiac index (CI) <1.8L/min/m^2

 -  active smoking Status

 -  patient with severe resting desaturation (repeatedly SpO2 <80%) or severe
 exercise-induced desaturation (SpO2 ≤75% for ≥10 minutes)