Evidence map›Paper›PMID 31358008›Full record

Trial reportRespiratory research2019

Bone and ocular safety of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler in COPD: a 52-week randomized study.

Edward M Kerwin, Gary T Ferguson, Mindy Mo, Kiernan DeAngelis, Paul Dorinsky

2 registry-linked trialsOpen access · goldAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Respiratory research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 16 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 7 pooled it
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02497001 phase3completednot on this map

A Randomized, Double-Blind, Parallel-Group, 24-Week, Chronic-Dosing, Multi-Center Study to Assess the Efficacy and Safety of PT010, PT003, and PT009 Compared With Symbicort® Turbuhaler® as an Active Control in Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease

TypeinterventionalSponsorPearl Therapeutics, Inc.Ran2015 to 2018Enrolled1,902ConditionsCOPDArmsBGF MDI 320/14.4/9.6 μg, GFF MDI (PT003) 14.4/9.6 μg, BFF MDI (PT009) 320/9.6 μg, Symbicort® Turbuhaler® (TBH) Inhalation Powder
NCT02536508 phase3completednot on this map

A Randomized, Double-Blind, Parallel-Group, 52-Week, Chronic-Dosing, Multi-Center Study to Assess the Safety and Tolerability of PT010, PT009 and PT003 in Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease

TypeinterventionalSponsorPearl Therapeutics, Inc.Ran2015 to 2017Enrolled627ConditionsCOPDArmsBGF MDI 320/14.4/9.6 μg, GFF MDI 14.4/9.6 μg, BFF MDI 320/9.6 μg
3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 7 syntheses or guidelines pooled it, 53 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Systematic review on long-term adverse effects of inhaled corticosteroids in the treatment of COPD.European respiratory review : an official journal of the European Respiratory Society · 2021
    Pooled it
  7. Pooled it
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Future Trends in Nebulized Therapies for Pulmonary Disease.Journal of personalized medicine · 2020
    Review
  15. Formoterol for the Treatment of Chronic Obstructive Pulmonary Disease.International journal of chronic obstructive pulmonary disease · 2020
    Review
  16. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Edward M KerwinClinical Research Institute of Southern Oregon, 3860 Crater Lake Avenue, Medford, OR, 97504, USA. ekerwin@criresearch.com.
Gary T FergusonPulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA.
Mindy MoFormerly of AstraZeneca, Morristown, NJ, USA.
Kiernan DeAngelisAstraZeneca, Durham, NC, USA.
Paul DorinskyAstraZeneca, Durham, NC, USA.
AstraZeneca (United States) · USClinical Research Institute · US

Funding

Pearl - a member of the AstraZeneca Group N/A
6 · The paper itself

Abstract

backgroundLong-term use of inhaled corticosteroids (ICSs) has been associated with increased risk of bone and ocular comorbidities. We evaluated the effects of the triple fixed-dose combination budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI), formulated using co-suspension delivery technology, on bone mineral density (BMD) and ocular safety in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD).

methodsIn this extension study, a subset of patients from the 24-week, phase III, randomized, double-blind KRONOS study (NCT02497001) continued treatment (BGF MDI 320/18/9.6 μg, budesonide/formoterol fumarate [BFF] MDI 320/9.6 μg or glycopyrrolate/formoterol fumarate [GFF] MDI 18/9.6 μg, as a non-steroidal comparator) for an additional 28 weeks. Primary endpoints were percentage change from baseline in lumbar spine BMD and change from baseline in lens opacities classification system III posterior subcapsular cataract (P) score, both at Week 52. Adverse events were also assessed.

resultsIn total, 456 patients were included in the safety population (53.1% male, mean age 62.8 years). Changes from baseline in lumbar spine BMD (least squares mean [LSM] range - 0.12 to 0.38%) and P score (LSM range 0.02-0.15) were small for all treatments. Both BGF MDI and BFF MDI were non-inferior to GFF MDI using margins of -2% (BMD) and 0.5 units (P score). The incidence of treatment-emergent adverse events (TEAEs)  was generally similar among groups. Rates of confirmed pneumonia were low overall (2.4%) and highest in the GFF MDI group (3.4%), followed by BGF MDI (2.1%) and BFF MDI (1.1%). There were no cumulative adverse effects of treatment over time as the incidence and types of TEAEs, were generally similar in the first 24 weeks of the study and after Week 24.

conclusionsIn patients with COPD, both ICS-containing therapies were non-inferior to GFF MDI for the primary BMD and ophthalmological endpoints. Changes from baseline in all three treatment groups over 52 weeks were small and not clinically meaningful. All treatments were well tolerated with no new or unexpected safety findings.

trial registrationClinicalTrials.gov NCT02536508. Registered 27 August 2015.

Indexed as

AgedAnti-Asthmatic AgentsBone DensityBronchodilator AgentsBudesonide, Formoterol Fumarate Drug CombinationCataractDouble-Blind MethodFemaleGlycopyrrolateHumansIntraocular PressureLens, CrystallineMaleMetered Dose InhalersMiddle AgedMuscarinic AntagonistsAnti-Asthmatic AgentsBronchodilator AgentsBudesonide, Formoterol Fumarate Drug CombinationGlycopyrrolateMuscarinic AntagonistsBGF MDIBone mineral densityInhaled corticosteroidLens opacityLOCS IIIMetered dose inhaler

Identifiers

PMID31358008
PMCPMC6664772
OpenAlexW2964806441

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.