Mechanisms of Vascular Damage in Patients With Chronic Obstructive Pulmonary Disease

Randomized Controlled Trial on the Cardiovascular Effects of Lung Volume Reduction Surgery in Patients With Chronic Obstructive Pulmonary Disease

A randomised controlled trial will be performed to evaluate the effects of lung volume reduction surgery (LVRS) in patients with COPD on systemic inflammation, oxidative stress, endothelial function, arterial stiffness and blood pressure. We hypothesize that LVRS will lead to a reduction of systemic inflammation, oxidative stress, arterial stiffness and blood pressure and to improved endothelial function.

For this purpose 30 patients with severe/very severe COPD (GOLD III-IV) and pulmonary emphysema who are to undergo LVRS will be randomised to one of two groups: group 1 receiving immediate LVRS and group 2 receiving LVRS after a delay of 3 months.

Measures of systemic inflammation, oxidative stress, endothelial function, arterial stiffness and blood pressure will be measured at baseline and 3 months after surgery and no surgery, respectively (group 2 receiving surgery only after a delay of 3 months will serve as control group) to investigate the effects of LVRS on the described outcomes.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Procedure: Lung volume reduction surgery

Detailed Description

Not desired

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland, 8091
    • Pulmonary Division, University Hospital of Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Dyspnea at rest or at minimal physical activity, severe limitation of exercise capacity (6-min walk distance < 350 m).
• Acceptance of an increased perioperative mortality (approximately 2 %) and/or morbidity (long lasting hospitalization due to prolonged air leaks)
• COPD (GOLD guidelines) with severe obstructive ventilatory defect (FEV1 <35% predicted)
• Functional aspects of lung emphysema, i.e. irreversible hyperinflation with a residual volume to total lung capacity ratio (RV/TLC) of >0.65 and an impaired total lung diffusion capacity (DLCO), usually < 40% predicted.
• Pulmonary emphysema confirmed by high resolution computer tomography

Exclusion criteria: - Current smokers

• Age > 75years
• "Vanishing" lung or diffuse lung emphysema on CT, FEV1 <20% predicted and DLCO <20% predicted, and hypercapnia (PaCO2 >7.3kPa)
• Overt active coronary artery disease, severe left ventricular function impairment
• Pulmonary hypertension with a mean pulmonary artery pressure >35 mmHg at rest
• Acute bronchopulmonary infection, bronchiectasis on high resolution tomography
• Pulmonary cachexia (body mass index <18kg/m2)
• Neoplastic disease with a life expectancy of less than 2 years
• Addiction to alcohol/drugs
• Relevant renal (creatinine >150ug/ml), active gastroenterological (GI-bleeding in the previous year, abnormal liver function, active inflammatory bowel disease) or active neurological disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lung volume reduction surgery; This group will receive lung volume reduction surgery	Procedure: Lung volume reduction surgery; Lung volume reduction surgery
No Intervention: No lung volume reduction surgery; This group will not receive LVRS during the 3 months of the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
1. Systemic inflammation 2. Vascular function	Before and 3 months after surgery/no surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
1. Oxidative stress 2. Blood pressure 3. Physical Activity 4. Lung function 5. Hypoxemia	Before and 3 months after surgery/no surgery

Collaborators and Investigators

• Sponsor: University of Zurich

Publications and helpful links

General Publications

• Clarenbach CF, Sievi NA, Brock M, Schneiter D, Weder W, Kohler M. Lung Volume Reduction Surgery and Improvement of Endothelial Function and Blood Pressure in Patients with Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial. Am J Respir Crit Care Med. 2015 Aug 1;192(3):307-14. doi: 10.1164/rccm.201503-0453OC.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: November 24, 2009
• First Submitted That Met QC Criteria: November 24, 2009
• First Posted (Estimate): November 25, 2009

Study Record Updates

• Last Update Posted (Estimate): October 16, 2014
• Last Update Submitted That Met QC Criteria: October 15, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: COPD-CVD2