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

Phase 2

Completed

• Conditions: Oxygen Deficiency; Pulmonary Arterial Hypertension; CTEPH
• Interventions: Drug: Oxygen

• Registration Number: NCT04207593
• Lead Sponsor: Heidelberg University

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.

Study Timeline

• Study Start: 2019-04-01
• Study First Submitted: 2019-12-17
• Study First Submitted QC: 2019-12-18
• Study First Posted: 2019-12-23
• Primary Completion: 2023-01-01
• Study Completion: 2023-01-10
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-18
• Last Update Posted: 2024-06-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
no-supplemental-oxygen group (control group)	Oxygen	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).
Oxygen Therapy provided	Oxygen	Patients will be divided in a supplemental-oxygen group (primary intervention group) throughout the study

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
pulmonary vascular resistance (PVR)	Change from baseline to 6 months	Right heart catheterization
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
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
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
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
cardiac output and ejection fraction (CO, HZV)	Change from baseline to 6 months	Right heart catheterization
Peak oxygen consumption	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
right atrial pressure	Change from baseline to 6 months	Right heart catheterization
cardiac index (CI)	Change from baseline to 6 months	Right heart catheterization
respiratory reserve	Change from baseline to 6 months	Cardiopulmonary exercise testing
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
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
systolic pulmonary arterial pressure	Change from baseline to 6 months	Right heart catheterization
Peak oxygen consumption/kg body weight	Change from baseline to 6 months	Cardiopulmonary exercise testing
Oxygen pulse	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
ventilatory threshold	Change from baseline to 6 months	Cardiopulmonary exercise testing

Trial Locations

Locations (1)

Centre for pulmonary hypertension of the Thoraxclinic at the University Hospital Heidelberg; 🇩🇪 Heidelberg, Germany