Impact of Pulmonary Endarterectomy on Sleep-Related Breathing Disorders in CTEPH: The IPES Trial

Study Purpose

Pulmonary hypertension (PH) has three main types, pre-capillary PH, post-capillary PH, and combined pre-capillary and post-capillary PH, and it is based on mean pulmonary arterial pressure (PAP) > 20 mmHg measured with a right heart catheterization (RHC). Chronic thromboembolic pulmonary hypertension (CTEPH) is mainly defined as a pre-capillary PH and classed as a Group IV PH. It was reported that 0.1-9.1% of individuals with pulmonary embolism develop CTEPH within two years after the initial diagnosis, and CTEPH is the only PH category that has a chance of being cured, mainly by pulmonary endarterectomy. Sleep-related breathing disorders (SRBD) are defined as obstructive sleep apnea (OSA) disorders, central sleep apnea (CSA) syndromes, sleep-related hypoventilation disorders, and sleep-related hypoxemia. An SRBD may also lead to an increase in PAP primarily during sleep and cause nocturnal hypoxemia. Although SRBDs were reported in patients with pre-capillary PH, most of the studies included patients with idiopathic PAH. Although the cause-and-effect relationship between pre-capillary PH and SRBDs is uncertain, it is known that mPAP may increase during sleep in patients with OSA . Less is known regarding the occurrence of SRBDs in CTEPH. Previously a few study showed relationship between SRBDs an CTEPH as the main type was OSA. Most of the studies evaluated preoperative occurance and incidance of SRBDs in CTEPH. Only one study performed post operative SRBD on a cardiorespiratory device was conducted the night before and one month after elective pulmonary endarterectomy. In our previous study we showed that severe nocturnal hypoxemia (NH) is highly prevelant in preoperative CTEPH patients and the most common two types of SRBD are OSA and isolated sleep related hypoxemia (ISRH) and age, mPAP and AHI are independent determinants of severe NH. (J. Clin. Med. 2023, 12, 4639 https://doi.org/10.3390/jcm12144639) In this present study we aimed to investigate occurrence of SRBDs and mortality 5 years after pulmonary endarterectomy operation.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Previously diagnosed with CTEPH according to radiology and right heart catheterization and eligible for surgery.

- Polisomnography test.

- Includes both criteria above.

Exclusion Criteria:

- do not volunter for study.

- exitus

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06060366
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Marmara University
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Sehnaz Olgun Yildizeli, Assoc Prof
Principal Investigator Affiliation	ICJME
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries	Turkey
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Sleep-Disordered Breathing, Chronic Thromboembolic Pulmonary Hypertension, Post Operative

Additional Details

This study planned as continuation study of ''Determinants of severe nocturnal hypoxemia in adults with chronic thromboembolic pulmonary hypertension and sleep related breathing disorders'' J. Clin. Med. 2023, 12, 4639 https://doi.org/10.3390/jcm12144639. Previously included patients (50 patients who were referred for pulmonary endarterectomy operation between 5 May 2017 and 7 February 2018.

- All participants underwent a computerized pulmonary angiography and RHC after that mismatch of perfusion defects detected in ventilation/perfusion scintigraphy (V/Q) despite 3 months of anticoagulant therapy.

- Patients with an mPAP > 20 mmHg measured with RHC were accepted having CTEPH PAWP≤15mmHg and PVR≥ 3 Wood Units were additional measurements suggestive of CTEPH.

- Eligible for surgery.

- Appropriate polisomnography test before surgery.

- Total sleep time should be >4 hours) planned to include current study.

1. Demographic data, body mass index (BMI), comorbid conditions, medications, supplementary oxygen treatment, preoperative echocardiography findings, RHC measurements, 6 min walk distance (SMWD), pulmonary function test, as well as carbon monoxide diffusion test (DLCO) measurements will be recorded. **MIR Spirolab II spirometry (Medical International Research, Rome, Italy) was used to test pulmonary function, including forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), diffusing capacity of the lung for DLCO in a body plethsmograph (CareFusion Type MasterScreen PFT, Hoechberg, Germany), and performance of an SMWD. All results were assessed in accordance with ATS recommendations. 2. A polisomnography test will perfomed to all participants (whether had pulmonary endarterectomy operation or followed up by medical treatment)

- All patients will hospitalized for polysomnographic monitoring using the NOX- A1 system (Nox Medical Inc.

, Reykjavik, Iceland). The PSG recording included an elec- troencephalogram (F4/M1, F3/M2, C4/M1, C3/M2, O2/M1, O1/M2), electro-oculogram, submental and tibialis electromyograms, as well as an electrocardiogram. Ventilatory monitoring included a nasal pressure detector using a nasal cannula/pressure transducer system and thoracoabdominal movement detection through two respiratory inductance plethysmography belts. A finger pulse oximeter detecting heart rate, SpO2, as well as body position and movement detection will also include. Participants with a total sleep time of less than 4 h will be offered a new PSG. Sleep stages and arousals will score based on 30 s epochs in accordance with The AASM Manual for the Scoring of Sleep and Associated Events 2.5 published by the American Academy of Sleep Medicine (AASM), independently of the patients' clinics, by a certified sleep physician. Apnea will define as an almost complete (≥ 90%) cessation of airflow, and hypopnea will define as a decrease in nasal pressure amplitude of 30% or more and/or thoraco-abdominal movement of at least 30% for at least 10 s if there will be a significant oxyhemoglobin desaturation (reduction of at least 3% from the immediately preceding baseline value) and/or arousal, according to the latest recommendations of the AASM.

- SRBDs defined according to the International Classification of Sleep Disorders (ICSD)-10 as obstructive sleep apnea (OSA; as an AHI ≥ 15 events/h), central sleep apnea with Cheyne-Stokes respiration (CSA-CSR; CSR pattern ≥ 50% of total sleep time with , (TST)), obesity hypoventilation syndrome (OHS), and isolated sleep-related hypoxemia (ISRH) (nocturnal oxyhemoglobin saturation (SpO2) < 88% for 5 min or more without OSA, CSA, or OHS) Severe NH was defined as SpO2 < 90% for more than 20% of total sleep time (TST) 3.

Cardiac evaluation will be performed by transthoracic-echocardiography (TTE) TTE based on the guidelines of the device (Epiq 7, Philips Healthcare, Andover, MA, USA) with a 3.5 MHz (S5-1) transducer. Digitally stored images will analyze offline (Xcelera, Philips). Based on the guidelines, the systolic and diastolic characteristics of the left and right heart will measure as recommended. Tricuspid regurgitation velocity and other echocardiographic signs will combine to assess the probability of PH as recommended in ERS guidelines

Arms & Interventions

Arms

: PE for CTEPH

CTEPH patients who were eligible for operation

: Medical treatment CTEPH

CTEPH patients who were not eligible for surgery of any reason and decided to follow up with medical treatment

Interventions

Procedure: - Pulmonary endarterectomy

removal of chronic thrombus from pulmonary arterial system

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