SOPHA: The Effect of Oxygen Therapy on 6MWD in PAH and CTEPH Patients With Hypoxemia
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Oxygen Therapy provided Patients will be divided in a supplemental-oxygen group (primary intervention group) throughout the study |
Drug: Oxygen
Study medication will be oxygen (O2) in diverse concentrations, titrated until a SaO2>90% or pO2 >60 mmHg is achieved, for 20 patients vs. no supplemental O2 for 20 patients over 90 ± 7 days. Patients of the control group will be offered to participate in the interventional treatment arm after they have terminated the control period (partial cross-over; secondary intervention group). After the end of the study it is up to the judgment of the investigator to prescribe oxygen to all patients who might benefit from the treatment.
Other Names:
|
| Sham Comparator: no-supplemental-oxygen group (control group) Patients of the control group will beginn the study without Oxygen Therapie and will be offered to participate in the interventional treatment arm after they have terminated the control period (partial cross-over; secondary intervention group). |
Drug: Oxygen
Study medication will be oxygen (O2) in diverse concentrations, titrated until a SaO2>90% or pO2 >60 mmHg is achieved, for 20 patients vs. no supplemental O2 for 20 patients over 90 ± 7 days. Patients of the control group will be offered to participate in the interventional treatment arm after they have terminated the control period (partial cross-over; secondary intervention group). After the end of the study it is up to the judgment of the investigator to prescribe oxygen to all patients who might benefit from the treatment.
Other Names:
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Outcome Measures
Primary Outcome Measures
- 6-minute Walking distance [Change from baseline to 6 months]
To determine the benefits for PH patients from a long-term oxygen therapy (LTOT) given continuously during ≥16h/day for 12 weeks, measured by improvement of exercise performance assessed by the 6 minute walking distance (6MWD).
Secondary Outcome Measures
- Quality of life: physical Summation score; short form health Survey 36 (score from 0-100; higher scores indicating better outcome) [Change from baseline to 6 months]
To investigate effects of oxygen treatment on QoL, physical Summation score measured with SF-36 questionnaire
- Quality of life: mental Summation score; short form health Survey 36 (score from 0-100; higher scores indicating better outcome) [Change from baseline to 6 months]
To investigate effects of oxygen treatment on QoL, mental Summation score measured with SF-36 questionnaire
- Clinical worsening; frequency and type of clinical worsening events [clinical worsening events from baseline to 6 months]
To assess time to worsening of oxygen saturation and time to clinical worsening
- cardiac index in liters per minute per square meter (of body surface area) /(CI) [Change from baseline to 6 months]
Assessment of Cardiac Index during RHC
- systolic pulmonary arterial pressure [Change from baseline to 6 months]
Right heart catheterization
- mean pulmonary arterial pressure [Change from baseline to 6 months]
Right heart catheterization
- pulmonary arterial wedge pressure [Change from baseline to 6 months]
Right heart catheterization
- right atrial pressure [Change from baseline to 6 months]
Right heart catheterization
- pulmonary vascular resistance (PVR) [Change from baseline to 6 months]
Right heart catheterization
- cardiac output and ejection fraction (CO, HZV) [Change from baseline to 6 months]
Right heart catheterization
- cardiac index (CI) [Change from baseline to 6 months]
Right heart catheterization
- blood gas analysis from pulmonary artery [Change from baseline to 6 months]
central venous saturation
- Change in systolic pulmonary arterial pressure [Change from baseline to 6 months]
Echocardiography and Stress Doppler Echocardiography
- Echocardiography and Stress Doppler Echocardiography [Change from baseline to 6 months]
right ventricular pump function
- Peak oxygen consumption [Change from baseline to 6 months]
Cardiopulmonary exercise testing
- Peak oxygen consumption/kg body weight [Change from baseline to 6 months]
Cardiopulmonary exercise testing
- oxygen Saturation [Change from baseline to 6 months]
Cardiopulmonary exercise testing
- oxygen equivalent [Change from baseline to 6 months]
Cardiopulmonary exercise testing
- Cardiopulmonary exercise testing [Change from baseline to 6 months]
carbon dioxide equivalent
- Oxygen pulse [Change from baseline to 6 months]
Cardiopulmonary exercise testing
- ventilatory threshold [Change from baseline to 6 months]
Cardiopulmonary exercise testing
- respiratory reserve [Change from baseline to 6 months]
Cardiopulmonary exercise testing
- World Health Organization functional classification [Change from baseline to 6 months]
Functional assessment of pulmonary hypertension
Eligibility Criteria
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 % ).
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men and women 18 years of age or older
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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
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patient is willing and able to provide written informed consent
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patient is willing and able to comply with the protocol, including required follow-up visits
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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
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patient has a stable functional class of PAH with no changes of medication during the last two weeks before inclusion
Exclusion Criteria
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Patient is a female who is pregnant, nursing, or of child bearing potential and is not on a reliable form of birth control
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patient with pulmonary venous hypertension
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significant functional limitation in lung function tests (FEV1 <60%,TLC <60%) and CT morphological signs of pulmonary disease
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significant left heart disease, requiring acute pharmacological or interventional treatment
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unstable conditions requiring pharmacological or other treatment, intensive care or relevant severe concomitant disease
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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.
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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
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active smoking Status
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patient with severe resting desaturation (repeatedly SpO2 <80%) or severe exercise-induced desaturation (SpO2 ≤75% for ≥10 minutes)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Centre for pulmonary hypertension of the Thoraxclinic at the University Hospital Heidelberg | Heidelberg | Germany | 69126 |
Sponsors and Collaborators
- Heidelberg University
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- 2018-11SO*