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

Primary Purpose

Oxygen Deficiency, Pulmonary Arterial Hypertension, CTEPH

Status

Recruiting

Phase

Phase 2

Locations

Germany

Study Type

Interventional

Intervention

Oxygen

About this trial

This is an interventional treatment trial for Oxygen Deficiency focused on measuring Oxygen, Pulmonary Arterial Hypertension, CTEPH, 6MWD

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Centre for pulmonary hypertension of the Thoraxclinic at the University Hospital HeidelbergRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Oxygen Therapy provided

no-supplemental-oxygen group (control group)

Arm Description

Patients will be divided in a supplemental-oxygen group (primary intervention group) throughout the study

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).

Outcomes

Primary Outcome Measures

6-minute Walking distance

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)

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)

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

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)

Assessment of Cardiac Index during RHC

systolic pulmonary arterial pressure

Right heart catheterization

mean pulmonary arterial pressure

Right heart catheterization

pulmonary arterial wedge pressure

Right heart catheterization

right atrial pressure

Right heart catheterization

pulmonary vascular resistance (PVR)

Right heart catheterization

cardiac output and ejection fraction (CO, HZV)

Right heart catheterization

cardiac index (CI)

Right heart catheterization

blood gas analysis from pulmonary artery

central venous saturation

Change in systolic pulmonary arterial pressure

Echocardiography and Stress Doppler Echocardiography

right ventricular pump function

Peak oxygen consumption

Cardiopulmonary exercise testing

Peak oxygen consumption/kg body weight

Cardiopulmonary exercise testing

oxygen Saturation

Cardiopulmonary exercise testing

oxygen equivalent

Cardiopulmonary exercise testing

carbon dioxide equivalent

Oxygen pulse

Cardiopulmonary exercise testing

ventilatory threshold

Cardiopulmonary exercise testing

respiratory reserve

Cardiopulmonary exercise testing

World Health Organization functional classification

Functional assessment of pulmonary hypertension

Full Information

NCT ID

NCT04207593

First Posted

December 17, 2019

Last Updated

July 12, 2022

Sponsor

Heidelberg University

1. Study Identification

Unique Protocol Identification Number

NCT04207593

Brief Title

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

Acronym

SOPHA

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

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Recruiting

Study Start Date

April 1, 2019 (Actual)

Primary Completion Date

December 2022 (Anticipated)

Study Completion Date

December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Heidelberg University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Oxygen Deficiency, Pulmonary Arterial Hypertension, CTEPH

Keywords

Oxygen, Pulmonary Arterial Hypertension, CTEPH, 6MWD

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study 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.

Allocation

Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Oxygen Therapy provided

Arm Type

Active Comparator

Arm Description

Patients will be divided in a supplemental-oxygen group (primary intervention group) throughout the study

Arm Title

no-supplemental-oxygen group (control group)

Arm Type

Sham Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Oxygen

Other Intervention Name(s)

Liquid oxygen

Intervention Description

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.

Primary Outcome Measure Information:

Title

6-minute Walking distance

Description

Time Frame

Change from baseline to 6 months

Secondary Outcome Measure Information:

Title

Quality of life: physical Summation score; short form health Survey 36 (score from 0-100; higher scores indicating better outcome)

Description

To investigate effects of oxygen treatment on QoL, physical Summation score measured with SF-36 questionnaire

Time Frame

Change from baseline to 6 months

Title

Quality of life: mental Summation score; short form health Survey 36 (score from 0-100; higher scores indicating better outcome)

Description

To investigate effects of oxygen treatment on QoL, mental Summation score measured with SF-36 questionnaire

Time Frame

Change from baseline to 6 months

Title

Clinical worsening; frequency and type of clinical worsening events

Description

To assess time to worsening of oxygen saturation and time to clinical worsening

Time Frame

clinical worsening events from baseline to 6 months

Title

cardiac index in liters per minute per square meter (of body surface area) /(CI)

Description

Assessment of Cardiac Index during RHC

Time Frame

Change from baseline to 6 months

Title

systolic pulmonary arterial pressure

Description

Right heart catheterization

Time Frame

Change from baseline to 6 months

Title

mean pulmonary arterial pressure

Description

Right heart catheterization

Time Frame

Change from baseline to 6 months

Title

pulmonary arterial wedge pressure

Description

Right heart catheterization

Time Frame

Change from baseline to 6 months

Title

right atrial pressure

Description

Right heart catheterization

Time Frame

Change from baseline to 6 months

Title

pulmonary vascular resistance (PVR)

Description

Right heart catheterization

Time Frame

Change from baseline to 6 months

Title

cardiac output and ejection fraction (CO, HZV)

Description

Right heart catheterization

Time Frame

Change from baseline to 6 months

Title

cardiac index (CI)

Description

Right heart catheterization

Time Frame

Change from baseline to 6 months

Title

blood gas analysis from pulmonary artery

Description

central venous saturation

Time Frame

Change from baseline to 6 months

Title

Change in systolic pulmonary arterial pressure

Description

Echocardiography and Stress Doppler Echocardiography

Time Frame

Change from baseline to 6 months

Title

Echocardiography and Stress Doppler Echocardiography

Description

right ventricular pump function

Time Frame

Change from baseline to 6 months

Title

Peak oxygen consumption

Description

Cardiopulmonary exercise testing

Time Frame

Change from baseline to 6 months

Title

Peak oxygen consumption/kg body weight

Description

Cardiopulmonary exercise testing

Time Frame

Change from baseline to 6 months

Title

oxygen Saturation

Description

Cardiopulmonary exercise testing

Time Frame

Change from baseline to 6 months

Title

oxygen equivalent

Description

Cardiopulmonary exercise testing

Time Frame

Change from baseline to 6 months

Title

Cardiopulmonary exercise testing

Description

carbon dioxide equivalent

Time Frame

Change from baseline to 6 months

Title

Oxygen pulse

Description

Cardiopulmonary exercise testing

Time Frame

Change from baseline to 6 months

Title

ventilatory threshold

Description

Cardiopulmonary exercise testing

Time Frame

Change from baseline to 6 months

Title

respiratory reserve

Description

Cardiopulmonary exercise testing

Time Frame

Change from baseline to 6 months

Title

World Health Organization functional classification

Description

Functional assessment of pulmonary hypertension

Time Frame

Change from baseline to 6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ekkehard Grünig, Prof., MD

Phone

06221 / 396 8053

ekkehard.gruenig@med.uni-heidelberg.de

First Name & Middle Initial & Last Name or Official Title & Degree

Benjamin Egenlauf, MD

Phone

06221 / 396 8078

Benjamin.Egenlauf@med.uni-heidelberg.de

Facility Information:

Facility Name

Centre for pulmonary hypertension of the Thoraxclinic at the University Hospital Heidelberg

City

Heidelberg

ZIP/Postal Code

69126

Country

Germany

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ekkehard Grünig, MD

Phone

+4962213968053

ekkehard.gruenig@med.uni-heidelberg.de

First Name & Middle Initial & Last Name & Degree

Ekkehard Grünig, MD

12. IPD Sharing Statement

Citations:

PubMed Identifier

28329240

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.

Results Reference

result

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

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