Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Effect of Oxygen Therapy on 6MWD in PAH and CTEPH Patients With Hypoxemia (SOPHA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04207593
Recruitment Status : Recruiting
First Posted : December 23, 2019
Last Update Posted : May 4, 2021
Sponsor:
Information provided by (Responsible Party):
Prof. Dr. med. Ekkehard Gruenig, Thoraxklinik-Heidelberg gGmbH

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
Oxygen Deficiency Pulmonary Arterial Hypertension CTEPH Drug: Oxygen 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Masking Description: PAH patients experiencing oxygen desaturations at rest and during physical activity, when O2 partial pressure is repeatedly <8 kPa (<60 mmHg; alternatively, 90% of O2 saturation). Patients will be divided in a supplemental-oxygen group (primary intervention group) and no-supplemental-oxygen group (control group). 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). Randomization will be performed in a 1:1 ratio. Randomization to one of the groups will be performed by block randomization. Randomization lists will be created by the data management using a computer to generate random numbers.
Primary Purpose: Treatment
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
Actual Study Start Date : April 1, 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021


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 Name: Liquid oxygen

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 Name: Liquid oxygen




Primary Outcome Measures :
  1. 6-minute Walking distance [ Time Frame: 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 :
  1. Quality of life: physical Summation score; short form health Survey 36 (score from 0-100; higher scores indicating better outcome) [ Time Frame: Change from baseline to 6 months ]
    To investigate effects of oxygen treatment on QoL, physical Summation score measured with SF-36 questionnaire

  2. Quality of life: mental Summation score; short form health Survey 36 (score from 0-100; higher scores indicating better outcome) [ Time Frame: Change from baseline to 6 months ]
    To investigate effects of oxygen treatment on QoL, mental Summation score measured with SF-36 questionnaire

  3. Clinical worsening; frequency and type of clinical worsening events [ Time Frame: clinical worsening events from baseline to 6 months ]
    To assess time to worsening of oxygen saturation and time to clinical worsening

  4. cardiac index in liters per minute per square meter (of body surface area) /(CI) [ Time Frame: Change from baseline to 6 months ]
    Assessment of Cardiac Index during RHC

  5. systolic pulmonary arterial pressure [ Time Frame: Change from baseline to 6 months ]
    Right heart catheterization

  6. mean pulmonary arterial pressure [ Time Frame: Change from baseline to 6 months ]
    Right heart catheterization

  7. pulmonary arterial wedge pressure [ Time Frame: Change from baseline to 6 months ]
    Right heart catheterization

  8. right atrial pressure [ Time Frame: Change from baseline to 6 months ]
    Right heart catheterization

  9. pulmonary vascular resistance (PVR) [ Time Frame: Change from baseline to 6 months ]
    Right heart catheterization

  10. cardiac output and ejection fraction (CO, HZV) [ Time Frame: Change from baseline to 6 months ]
    Right heart catheterization

  11. cardiac index (CI) [ Time Frame: Change from baseline to 6 months ]
    Right heart catheterization

  12. blood gas analysis from pulmonary artery [ Time Frame: Change from baseline to 6 months ]
    central venous saturation

  13. Change in systolic pulmonary arterial pressure [ Time Frame: Change from baseline to 6 months ]
    Echocardiography and Stress Doppler Echocardiography

  14. Echocardiography and Stress Doppler Echocardiography [ Time Frame: Change from baseline to 6 months ]
    right ventricular pump function

  15. Peak oxygen consumption [ Time Frame: Change from baseline to 6 months ]
    Cardiopulmonary exercise testing

  16. Peak oxygen consumption/kg body weight [ Time Frame: Change from baseline to 6 months ]
    Cardiopulmonary exercise testing

  17. oxygen Saturation [ Time Frame: Change from baseline to 6 months ]
    Cardiopulmonary exercise testing

  18. oxygen equivalent [ Time Frame: Change from baseline to 6 months ]
    Cardiopulmonary exercise testing

  19. Cardiopulmonary exercise testing [ Time Frame: Change from baseline to 6 months ]
    carbon dioxide equivalent

  20. Oxygen pulse [ Time Frame: Change from baseline to 6 months ]
    Cardiopulmonary exercise testing

  21. ventilatory threshold [ Time Frame: Change from baseline to 6 months ]
    Cardiopulmonary exercise testing

  22. respiratory reserve [ Time Frame: Change from baseline to 6 months ]
    Cardiopulmonary exercise testing

  23. World Health Organization functional classification [ Time Frame: Change from baseline to 6 months ]
    Functional assessment of pulmonary hypertension



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04207593


Contacts
Layout table for location contacts
Contact: Ekkehard Grünig, Prof., MD 06221 / 396 8053 ekkehard.gruenig@med.uni-heidelberg.de
Contact: Benjamin Egenlauf, MD 06221 / 396 8078 Benjamin.Egenlauf@med.uni-heidelberg.de

Locations
Layout table for location information
Germany
Centre for pulmonary hypertension of the Thoraxclinic at the University Hospital Heidelberg Recruiting
Heidelberg, Germany, 69126
Contact: Ekkehard Grünig, MD    +4962213968053    ekkehard.gruenig@med.uni-heidelberg.de   
Principal Investigator: Ekkehard Grünig, MD         
Sponsors and Collaborators
Heidelberg University
  Study Documents (Full-Text)

Documents provided by Prof. Dr. med. Ekkehard Gruenig, Thoraxklinik-Heidelberg gGmbH:
Publications of Results:
Layout table for additonal information
Responsible Party: Prof. Dr. med. Ekkehard Gruenig, Prof. Dr. med. Ekkehard Grünig; Head of centre for pulmonary hypertension, Thoraxklinik-Heidelberg gGmbH
ClinicalTrials.gov Identifier: NCT04207593    
Other Study ID Numbers: 2018-11SO*
First Posted: December 23, 2019    Key Record Dates
Last Update Posted: May 4, 2021
Last Verified: April 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Prof. Dr. med. Ekkehard Gruenig, Thoraxklinik-Heidelberg gGmbH:
Oxygen
Pulmonary Arterial Hypertension
CTEPH
6MWD
Additional relevant MeSH terms:
Layout table for MeSH terms
Pulmonary Arterial Hypertension
Hypertension
Hypoxia
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Signs and Symptoms, Respiratory