Clinical trial NCT04207593: The Effect of Oxygen Therapy on 6MWD in PAH and CTEPH Patients With Hypoxemia
Official title: Prospective, Randomized, Controlled Trial of the Effect of Long-term Oxygen Therapy on 6-minute Walking Distance, Clinical Parameters and Hemodynamics in Patients With PAH and CTEPH
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Oxygen Deficiency
Pulmonary Arterial Hypertension
CTEPH
Keywords: Oxygen
Pulmonary Arterial Hypertension
CTEPH
6MWD
Lead sponsor: Heidelberg University
Sponsor class: OTHER
First posted: 2019-12-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: 6-minute Walking distance
timeFrame: Change from baseline to 6 months
Secondary outcomes:
measure: Quality of life: physical Summation score; short form health Survey 36 (score from 0-100; higher scores indicating better outcome)
timeFrame: Change from baseline to 6 months
measure: Quality of life: mental Summation score; short form health Survey 36 (score from 0-100; higher scores indicating better outcome)
timeFrame: Change from baseline to 6 months
measure: Clinical worsening; frequency and type of clinical worsening events
timeFrame: clinical worsening events from baseline to 6 months
measure: cardiac index in liters per minute per square meter (of body surface area) /(CI)
timeFrame: Change from baseline to 6 months
measure: systolic pulmonary arterial pressure
timeFrame: Change from baseline to 6 months
measure: mean pulmonary arterial pressure
timeFrame: Change from baseline to 6 months
measure: pulmonary arterial wedge pressure
timeFrame: Change from baseline to 6 months
measure: right atrial pressure
timeFrame: Change from baseline to 6 months
measure: pulmonary vascular resistance (PVR)
timeFrame: Change from baseline to 6 months
measure: cardiac output and ejection fraction (CO, HZV)
timeFrame: Change from baseline to 6 months
measure: cardiac index (CI)
timeFrame: Change from baseline to 6 months
measure: blood gas analysis from pulmonary artery
timeFrame: Change from baseline to 6 months
measure: Change in systolic pulmonary arterial pressure
timeFrame: Change from baseline to 6 months
measure: Echocardiography and Stress Doppler Echocardiography
timeFrame: Change from baseline to 6 months
measure: Peak oxygen consumption
timeFrame: Change from baseline to 6 months
measure: Peak oxygen consumption/kg body weight
timeFrame: Change from baseline to 6 months
measure: oxygen Saturation
timeFrame: Change from baseline to 6 months
measure: oxygen equivalent
timeFrame: Change from baseline to 6 months
measure: Cardiopulmonary exercise testing
timeFrame: Change from baseline to 6 months
measure: Oxygen pulse
timeFrame: Change from baseline to 6 months
measure: ventilatory threshold
timeFrame: Change from baseline to 6 months
measure: respiratory reserve
timeFrame: Change from baseline to 6 months
measure: World Health Organization functional classification
timeFrame: Change from baseline to 6 months
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: Centre for pulmonary hypertension of the Thoraxclinic at the University Hospital Heidelberg
Study officials:
References:
citation: Ulrich S, Hasler ED, Saxer S, Furian M, Muller-Mottet S, Keusch S, Bloch KE. Effect of breathing oxygen-enriched air on exercise performance in patients with precapillary pulmonary hypertension: randomized, sham-controlled cross-over trial. Eur Heart J. 2017 Apr 14;38(15):1159-1168. doi: 10.1093/eurheartj/ehx099.