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

NCT ID: NCT04207593

Last Updated: 2024-06-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-01
• Study Completion Date: 2023-01-10

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.

Conditions

Oxygen Deficiency; Pulmonary Arterial Hypertension; CTEPH

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Oxygen Therapy provided

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

Group Type: ACTIVE_COMPARATOR

Oxygen

Intervention Type: DRUG

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.

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).

Group Type: SHAM_COMPARATOR

Oxygen

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Liquid oxygen

Eligibility Criteria

Inclusion Criteria

• men and women 18 years of age or older

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

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Heidelberg University

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. med. Ekkehard Gruenig

Prof. Dr. med. Ekkehard Grünig; Head of centre for pulmonary hypertension

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

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

Heidelberg, , Germany

Countries

Germany

References

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.

Reference Type: RESULT

PMID: 28329240 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2018-11SO*

Identifier Type: -

Identifier Source: org_study_id