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Pulmonary Disease, Chronic ObstructivePhase 3NCT01691885

RELOVAIR® Lung Deflation Study

A Phase 3 study testing Fluticasone Furoate and Vilanterol in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 40 years and older
Conditions the study is for
Pulmonary Disease, Chronic Obstructive
What is being tested?
Fluticasone Furoate and Vilanterol
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
45 participants
Where
1 siteUnited Kingdom
Study dates
Nov 2012to Aug 2014
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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).
Show all 22Show fewer
  • 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.
  • Inclusion of these patients with events over 1 month prior to screening will be based on physician's judgment.
  • History of malignancy within the past 5 years, other than non-melanoma skin cancer.
  • End stage chronic renal disease: Subjects will be excluded if on renal replacement therapy (hemodialysis or peritoneal). Drug/food allergy: Subjects with a history of hypersensitivity to any of the study medications (e.g. beta-agonists, corticosteroid) or components of the inhalation powder (e.g. lactose, magnesium stearate). In addition, patients with a history of severe milk protein allergy that, in the opinion of the study physician, contraindicates the subject's participation will also be excluded.
  • Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years.
  • Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen should not be initiated during the trial.
  • Questionable validity of consent: Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study or the potential compliance to study procedures.
  • Additional medication: Use of an investigational device or investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
  • Use of the following medications is not permitted within the following timeframes: Prohibited Treatment: Depot corticosteroids, Time: 12 weeks; Prohibited Treatment: Cytochrome P450 3A4 strong inhibitors including but not limited to antiretrovirals (protease inhibitors) (e.g., indinavir, nelfinavir, ritonavir, saquinavir, atazanavir); imidazole and triazole anti- fungals (e.g., ketaconazole, itraconazole, voriconazole); clarithromycin, telithromycin, troleandomycin, mibefradil, cyclosporin, nefazodone, Time: 6 weeks, Grapefruit is allowed up to Visit 1, then limited to no more than one glass of grapefruit juice (250 mL/8 ounces) or one grapefruit per day (The use of cytochrome p450 3A4 inhibitors and inducers in the presence of significant liver impairment will result in the participant being excluded from the trial); Prohibited Treatment: Systemic, oral, parenteral (intra-articular) corticosteroids, Time: 30 days; Prohibited Treatment: Antibiotics, Time: 6 weeks; Prohibited Treatment: Inhaled corticosteroids, Time: 2 weeks; Inhaled ICS/LABA combination products, Time: 2 weeks; Prohibited Treatment: Long-acting anticholinergics (e.g., tiotropium), Time: 4 days; Prohibited Treatment: PDE-4 inhibitors (e.g., roflumilast), Time: 1 week; Prohibited Treatment: Oral leukotriene inhibitors (e.g., zafirlukast, montelukast, zileuton), Time: 48 hours; Prohibited Treatment: Inhaled long acting beta2-agonists (LABA) (e.g., salmeterol), Time: 48 hours; Prohibited Treatment: Oral beta-agonists, Time: 48 hours; Prohibited Treatment: Inhaled sodium cromoglycate or nedocromil sodium, Time: 24 hours; Prohibited Treatment Ipratropium/albuterol (salbutamol) combination product, Time: 6 hours; Prohibited Treatment: Short-acting anti-cholinergics (e.g., ipratropium bromide), Time: 6 hours (ipratropium will be supplied for rescue during the study, in inhaled or nebulized form); Prohibited Treatment: Theophylline preparations, Time: 48 hours; Prohibited Treatment: Inhaled short-acting beta2-agonists, Time: 6 hours (albuterol/salbutamol will be supplied for rescue during the study, in inhaled or nebulized form)

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site
  • GSK Investigational Site

    London, E2 9JX

Other trials in United Kingdom

About this study

Official title: A Randomised, Double-Blind, Placebo-Controlled, Cross-Over, Single-Centre Study to Investigate the Acute Lung Deflation Effects of Fluticasone Furoate/Vilanterol Inhalation Powder 100/25mcg Once Daily on Cardiac Biventricular Function and Arterial Stiffness in Adults With Chronic Obstructive Pulmonary Disease (COPD)

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.

Read the detailed description

This will be a Phase IIIb, randomised, double-blind, placebo-controlled, cross-over, single-centre study to investigate the acute effects of FF/VI inhalation powder 100/25mcg QD in lung deflation on cardiac biventricular function and arterial stiffness in adults with COPD.

Subjects will visit the clinic a minimum of 4 times over a 28-day period with a further contact which can be either a telephone contact or clinic visit (Visit/Contact 4). A 7-day run-in period will be followed by two 7-day (maximum 14-day) treatment periods separated by a 7(±2) day wash-out period. The first dose of treatment will be taken the day after randomisation. A safety Follow-up contact (either visit or telephone) will occur 7(±2) days post the last treatment day.

Subjects will be prescribed appropriate COPD therapy at the end of Treatment Visit 5, if required. There are no plans to provide the study drug for compassionate use following study completion.

It is planned to have 44 completed evaluable subjects. Subjects who withdraw early will be replaced. In order to ensure 44 evaluable subjects, assuming a 10% protocol deviation rate, 49 subjects will be randomised. The total duration of subject participation, including the follow-up period, will be approximately 36 days.

Being tested
Fluticasone Furoate, Vilanterol
Medical subject headings
Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fluticasone FuroateDrug

    Also called RELOVAIR®

    100mcg Once daily

  • VilanterolDrug

    Also called RELOVAIR®

    25mcg Once daily

Study groups in NCT01691885
Study groupRoleWhat they receive
A/BExperimentalPlacebo followed by Fluticasone Furoate Vilanterol Combination
Receives: Drug: Fluticasone Furoate; Drug: Vilanterol
B/APlacebo comparatorFluticasone Furoate Vilanterol Combination followed by Placebo
Receives: Drug: Fluticasone Furoate; Drug: Vilanterol

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline and end of Treatment Period (7 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Sep 2012 (estimated)
  2. Study startNov 2012
  3. Primary completionJul 2014
  4. Study completionAug 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01691885
Sponsor's protocol ID
116601
Status last verified
Aug 2016
First submitted
30 Aug 2012
Last updated
27 Oct 2016
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

  • 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.

    PubMed 31833441
  • 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.

    PubMed 26550687

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Fluticasone Furoate and Vilanterol in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change From Baseline in Right Ventricular End Diastolic Volume Index (RVEDVI) at the End of the Overall Treatment Period (time frame: Baseline and end of Treatment Period (7 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01691885, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2016.

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