RELOVAIR® Lung Deflation Study

NCT01691885 | Completed Phase 3 Results

• 1 other identifier: 116601
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the study is to test the hypothesis that lung hyperinflation contributes to cardiac dysfunction in COPD and that the treatment of lung deflation with FF/VI Inhalation Powder 100/25 mcg administered once daily (QD) will result in the reversal of this cardiac dysfunction compared with placebo. This will be assessed by measures of right and left global and regional systolic and diastolic cardiac function as assessed using a 30 minute CMR. A secondary objective will be to investigate the effect of FF/VI inhalation powder 100/25mcg QD on measures of arterial stiffness in the form of pulse wave analysis and distensability in the pulmonary and systemic circulation.

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline in Right Ventricular End Diastolic Volume Index (RVEDVI) at the End of the Overall Treatment Period

  RVEDVI is a measure of the volume of blood in the right ventricle at the end of diastole, normalized over body surface area and was measured using Cardiac Magnetic Resonance (CMR) imaging. RVEDVI is calculated as the right ventricular end diastolic volume (RDEDV) divided by the body surface area (BSA). The change from Baseline in RVEDVI was analyzed using a mixed model analysis with period, treatment group, and Baseline RVEDVI fitted as fixed effects and participants fitted as a random effect. The Baseline is defined as the assessment performed pre-dose at Day 1 of Treatment Period 1. The change from Baseline is calculated as the RVEDVI value at the end of each treatment period minus the Baseline value. The Per Protocol (PP) Population was comprised of all participants in the modified intent-to-treat (mITT) Population not identified as having deviations considered to impact the primary efficacy analysis.

  Baseline and end of Treatment Period (7 days)

Study Arms (2)

A/B

EXPERIMENTAL

Placebo followed by Fluticasone Furoate Vilanterol Combination

Drug: Fluticasone Furoate; Drug: Vilanterol

B/A

PLACEBO COMPARATOR

Fluticasone Furoate Vilanterol Combination followed by Placebo

Drug: Fluticasone Furoate; Drug: Vilanterol

Interventions

Fluticasone Furoate DRUG

100mcg Once daily

Also known as: RELOVAIR®

A/B; B/A

Vilanterol DRUG

25mcg Once daily

Also known as: RELOVAIR®

A/B; B/A

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type of subject: Outpatient.
• Informed consent: Subjects must give their signed and dated written informed consent to participate.
• Gender: Males or females. Female subjects must be post-menopausal or using a highly effective method for avoidance of pregnancy. The decision to include or exclude women of childbearing potential may be made at the discretion of the investigator in accordance with local practice in relation to adequate contraception.
• Age 40 and above
• Smoking history of at least 15 pack years. Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1.
• Established diagnosis of COPD according to ATS/ERS criteria: Subjects with a measured post-albuterol/salbutamol FEV1 less than 70% of predicted normal values; FEV1/FVC ratio after bronchodilator less than 0.7; Post-bronchodilator spirometry will be performed approximately 15 minutes after the subject has self-administered 4 inhalations (i.e., total 400mcg) of salbutamol via an MDI with a valved-holding chamber. The FEV1/FVC ratio and FEV1 percent predicted values will be calculated; MRC SCORE greater than 1
• Residual Volume (RVol) greater than and equal to 20% above predicted value demonstrating evidence of reversibility post bronchodilator of greater than and equal to 7.5% predicted.

You may not qualify if:

• Pregnancy: Women who are pregnant or lactating.
• Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of asthma are eligible if they also have a current diagnosis of COPD).
• α1-antitrypsin deficiency: Subjects with known α-1 antitrypsin deficiency as the underlying cause of COPD
• Other respiratory disorders: Subjects with active tuberculosis or lung cancer as well as clinically significant bronchiectasis, sarcoidosis, pulmonary fibrosis, interstitial lung diseases or other active pulmonary diseases. Pulmonary hypertension from causes other than COPD.
• Lung resection or transplantation: Subjects with lung volume reduction surgery within the 12 months prior to Screening or having had a lung transplant or pneumonectomy.
• A moderate/severe COPD exacerbation that has not resolved at least 14 days prior to screening and at least 30 days following the last dose of oral corticosteroids (if applicable).
• Lower respiratory tract infection: Subjects with lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to screening.
• Pulmonary Rehabilitation: Patients to be excluded if they have been in the acute phase of pulmonary rehabilitation in the 4 weeks prior to screening
• Current severe heart failure (New York Heart Association class IV) \[New York HeartAssociation, 1994\]. Subjects will also be excluded if they have a known ejection fraction of less than 30%.
• Abnormal and clinically significant 12-lead ECG
• Other systemic inflammatory conditions associated with chronic inflammation in the opinion of the investigator (e.g. rheumatoid arthritis, connective tissue disorders and Inflammatory Bowel Disease)
• Other significant diseases / abnormalities: Any life-threatening condition with life expectancy greater than 1 year, other than vascular disease or COPD, that might prevent the subject from completing the study.
• Coronary Artery Bypass Grafting (CABG) in the 6 months prior to screening.
• Myocardial infarction, cerebrovascular event or coronary artery intervention other than CABG in the 1 month prior to screening.
• History of malignancy within the past 5 years, other than non-melanoma skin cancer.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

London, E2 9JX, United Kingdom

Location

Related Publications (2)

• Khanji MY, Stone IS, Boubertakh R, Cooper JA, Barnes NC, Petersen SE. Chronic Obstructive Pulmonary Disease as a Predictor of Cardiovascular Risk: A Case-Control Study. COPD. 2020 Feb;17(1):81-89. doi: 10.1080/15412555.2019.1694501. Epub 2019 Dec 13.

  PMID: 31833441 DERIVED

• Stone IS, Barnes NC, James WY, Midwinter D, Boubertakh R, Follows R, John L, Petersen SE. Lung Deflation and Cardiovascular Structure and Function in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial. Am J Respir Crit Care Med. 2016 Apr 1;193(7):717-26. doi: 10.1164/rccm.201508-1647OC.

  PMID: 26550687 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

fluticasone furoate; vilanterol

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2012
• First Posted: September 25, 2012
• Study Start: November 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: August 1, 2014
• Last Updated: October 27, 2016
• Results First Posted: April 7, 2015

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)