Exubera Large Simple Trial To Evaluate Long-Term Pulmonary And Cardiovascular Safety (VOLUME)

An International, Multicenter, Large Simple Trial To Evaluate The Long-Term Pulmonary And Cardiovascular Safety Of Exubera In Patients With Diabetes Mellitus

The purpose of this study is to evaluate the long-term pulmonary and cardiovascular safety of Exubera in routine clinical practice.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes Care; Drug: Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes Care

Detailed Description

Pfizer announced in October 2007 that it would stop marketing Exubera. At that time, Pfizer committed to continued marketing until it returned the licensing rights for the technology to Nektar. Following the announcement, enrollment was halted. Subjects already enrolled and receiving treatment at the time of the halt in enrollment could continue in the study in accordance with the protocol. Nektar, the company from which Pfizer licensed Exubera, announced on April 9, 2008 that it had stopped its search for a new marketing partner. Accordingly, there will be no commercial availability of Exubera. As a result, an amendment was filed on April 16, 2008 specifying that all subjects randomized to Exubera had to be transitioned to usual diabetes care, and all study subjects followed for serious adverse events for 6 months. In accordance with this amendment, study A2171069 was terminated on April 29, 2009. Neither safety nor efficacy reasons were the cause of the study termination.

• Study Type: Interventional
• Enrollment (Actual): 1976
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Aschaffenburg, Germany, 63739
    • Pfizer Investigational Site
  • Bad Doberan, Germany, 18209
    • Pfizer Investigational Site
  • Bad Groenenbach, Germany, 87730
    • Pfizer Investigational Site
  • Bad Oeynhausen, Germany, 32549
    • Pfizer Investigational Site
  • Bad Staffelstein, Germany, 96231
    • Pfizer Investigational Site
  • Berlin, Germany, 13355
    • Pfizer Investigational Site
  • Berlin, Germany, 12247
    • Pfizer Investigational Site
  • Bonn, Germany, 53179
    • Pfizer Investigational Site
  • Chemnitz, Germany, 09130
    • Pfizer Investigational Site
  • Datteln, Germany, 45711
    • Pfizer Investigational Site
  • Dortmund, Germany, 44339
    • Pfizer Investigational Site
  • Dortmund, Germany, 44137
    • Pfizer Investigational Site
  • Eisenach, Germany, 99817
    • Pfizer Investigational Site
  • Emden, Germany, 26725
    • Pfizer Investigational Site
  • Essen, Germany, 45329
    • Pfizer Investigational Site
  • Esslingen, Germany, 73728
    • Pfizer Investigational Site
  • Falkensee, Germany, 14612
    • Pfizer Investigational Site
  • Friedberg, Germany, 86316
    • Pfizer Investigational Site
  • Fulda, Germany, 36037
    • Pfizer Investigational Site
  • Hagen, Germany, 58091
    • Pfizer Investigational Site
  • Hamburg, Germany, 21073
    • Pfizer Investigational Site
  • Hamburg, Germany, 22041
    • Pfizer Investigational Site
  • Hohenmoelsen, Germany, 06679
    • Pfizer Investigational Site
  • Jena, Germany, 07743
    • Pfizer Investigational Site
  • Koeln, Germany, 51069
    • Pfizer Investigational Site
  • Leverkusen, Germany, 51371
    • Pfizer Investigational Site
  • Mahlberg, Germany, 77972
    • Pfizer Investigational Site
  • Mannheim, Germany, 68161
    • Pfizer Investigational Site
  • Markdorf, Germany, 88677
    • Pfizer Investigational Site
  • Marl, Germany, 45770
    • Pfizer Investigational Site
  • Meissen, Germany, 01662
    • Pfizer Investigational Site
  • Muenster, Germany, 48145
    • Pfizer Investigational Site
  • Muenster, Germany, 48153
    • Pfizer Investigational Site
  • Neuwied, Germany, 56564
    • Pfizer Investigational Site
  • Nuernberg, Germany, 90480
    • Pfizer Investigational Site
  • Reinfeld, Germany, 23858
    • Pfizer Investigational Site
  • Riesa, Germany, 01587
    • Pfizer Investigational Site
  • Schluechtern, Germany, 36381
    • Pfizer Investigational Site
  • Siegen, Germany, 57072
    • Pfizer Investigational Site
  • Suhl, Germany, 98529
    • Pfizer Investigational Site
  • Villingen-Schwenningen, Germany, 78054
    • Pfizer Investigational Site
  • Wangen, Germany, 88239
    • Pfizer Investigational Site
  • Wangen I. Allgaeu, Germany, 88239
    • Pfizer Investigational Site
  • Warburg, Germany, 34414
    • Pfizer Investigational Site
• Puerto Rico
  • Manati, Puerto Rico, 00674
    • Pfizer Investigational Site
• Sweden
  • Boras, Sweden, 503 30
    • Pfizer Investigational Site
  • Forshaga, Sweden, 667 32
    • Pfizer Investigational Site
  • Goteborg, Sweden, 41345
    • Pfizer Investigational Site
  • Lilla Edet, Sweden, 46330
    • Pfizer Investigational Site
• United Kingdom
  • Airdrie, United Kingdom, ML6 0JS
    • Pfizer Investigational Site
  • Bath, United Kingdom, BA2 3HT
    • Pfizer Investigational Site
  • Bath, United Kingdom, BA2 4BY
    • Pfizer Investigational Site
  • Birmingham, United Kingdom, B37 7TR
    • Pfizer Investigational Site
  • Leicester, United Kingdom, LE1 5WW
    • Pfizer Investigational Site
  • Newcastle Upon Tyne, United Kingdom, NE15 6TQ
    • Pfizer Investigational Site
  • Newcastle Upon Tyne, United Kingdom, NE3 3QJ
    • Pfizer Investigational Site
  • Westbury, United Kingdom, BA13 3JD
    • Pfizer Investigational Site
  • Derbyshire
    • Chesterfield, Derbyshire, United Kingdom, S40 4TF
      • Pfizer Investigational Site
  • Middlesex
    • Ashford, Middlesex, United Kingdom, TW15 3EA
      • Pfizer Investigational Site
  • Sheffield
    • Dronfield, Sheffield, United Kingdom, S18 1RU
      • Pfizer Investigational Site
  • Surrey
    • Weybridge, Surrey, United Kingdom, KT15 2BH
      • Pfizer Investigational Site
    • Woking, Surrey, United Kingdom, GU22 7EY
      • Pfizer Investigational Site
  • Warwickshire
    • Rugby, Warwickshire, United Kingdom, CV22 5PX
      • Pfizer Investigational Site
  • Wiltshire
    • Warminster, Wiltshire, United Kingdom, BA12 9AA
      • Pfizer Investigational Site
  • Yorkshire
    • Sheffield, Yorkshire, United Kingdom, S7 2DW
      • Pfizer Investigational Site
• United States
  • Alabama
    • Bay Minette, Alabama, United States, 36507-4185
      • Pfizer Investigational Site
    • Fairhope, Alabama, United States, 36532
      • Pfizer Investigational Site
    • Graysville, Alabama, United States, 35073
      • Pfizer Investigational Site
    • Pell City, Alabama, United States, 35125
      • Pfizer Investigational Site
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Pfizer Investigational Site
    • Phoenix, Arizona, United States, 85028
      • Pfizer Investigational Site
    • Phoenix, Arizona, United States, 85029
      • Pfizer Investigational Site
  • Arkansas
    • Forrest City, Arkansas, United States, 72335
      • Pfizer Investigational Site
    • Searcy, Arkansas, United States, 72143
      • Pfizer Investigational Site
  • California
    • Cudahy, California, United States, 90201
      • Pfizer Investigational Site
    • El Cajon, California, United States, 92019
      • Pfizer Investigational Site
    • Huntington Beach, California, United States, 92648
      • Pfizer Investigational Site
    • Rolling Hills Estates, California, United States, 90274
      • Pfizer Investigational Site
    • San Jose, California, United States, 95116
      • Pfizer Investigational Site
    • Santa Ana, California, United States, 92704
      • Pfizer Investigational Site
    • Westminster, California, United States, 92683
      • Pfizer Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80219
      • Pfizer Investigational Site
  • Connecticut
    • Milford, Connecticut, United States, 06460
      • Pfizer Investigational Site
  • Delaware
    • Wilmington, Delaware, United States, 19806
      • Pfizer Investigational Site
  • Florida
    • Boca Raton, Florida, United States, 33433
      • Pfizer Investigational Site
    • Clearwater, Florida, United States, 33756
      • Pfizer Investigational Site
    • Debary, Florida, United States, 32713
      • Pfizer Investigational Site
    • Gainesville, Florida, United States, 32605
      • Pfizer Investigational Site
    • Green Cove Springs, Florida, United States, 32043
      • Pfizer Investigational Site
    • Hollywood, Florida, United States, 33021
      • Pfizer Investigational Site
    • Kissimmee, Florida, United States, 34743
      • Pfizer Investigational Site
    • Kissimmee, Florida, United States, 34741
      • Pfizer Investigational Site
    • Marianna, Florida, United States, 32446
      • Pfizer Investigational Site
    • Merritt Island, Florida, United States, 32952
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33144
      • Pfizer Investigational Site
    • Niceville, Florida, United States, 32578
      • Pfizer Investigational Site
    • Opa Locka, Florida, United States, 33054-3818
      • Pfizer Investigational Site
    • Orange City, Florida, United States, 32763
      • Pfizer Investigational Site
    • Ormond Beach, Florida, United States, 32174
      • Pfizer Investigational Site
    • Pembroke Pines, Florida, United States, 33027
      • Pfizer Investigational Site
    • Plantation, Florida, United States, 33324
      • Pfizer Investigational Site
    • Port Charlotte, Florida, United States, 33952
      • Pfizer Investigational Site
    • Tampa, Florida, United States, 33624
      • Pfizer Investigational Site
    • Tampa, Florida, United States, 33607
      • Pfizer Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Pfizer Investigational Site
    • Atlanta, Georgia, United States, 30318-2513
      • Pfizer Investigational Site
    • Conyers, Georgia, United States, 30013
      • Pfizer Investigational Site
    • Decatur, Georgia, United States, 30035
      • Pfizer Investigational Site
    • Warner Robins, Georgia, United States, 31088
      • Pfizer Investigational Site
  • Idaho
    • Boise, Idaho, United States, 83704
      • Pfizer Investigational Site
  • Illinois
    • Greenville, Illinois, United States, 62246
      • Pfizer Investigational Site
    • Libertyville, Illinois, United States, 60048
      • Pfizer Investigational Site
  • Indiana
    • Fishers, Indiana, United States, 46038
      • Pfizer Investigational Site
    • Indianapolis, Indiana, United States, 46229
      • Pfizer Investigational Site
    • Indianapolis, Indiana, United States, 46254-5472
      • Pfizer Investigational Site
  • Iowa
    • Des Moines, Iowa, United States, 50315
      • Pfizer Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States, 40258
      • Pfizer Investigational Site
    • Mount Sterling, Kentucky, United States, 40353
      • Pfizer Investigational Site
  • Louisiana
    • Bossier City, Louisiana, United States, 71111
      • Pfizer Investigational Site
  • Maine
    • Auburn, Maine, United States, 04210
      • Pfizer Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Pfizer Investigational Site
    • Elkton, Maryland, United States, 21921
      • Pfizer Investigational Site
    • Glen Burnie, Maryland, United States, 21061
      • Pfizer Investigational Site
    • Wheaton, Maryland, United States, 20902
      • Pfizer Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02110
      • Pfizer Investigational Site
    • Plymouth, Massachusetts, United States, 02360
      • Pfizer Investigational Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Pfizer Investigational Site
    • Battle Creek, Michigan, United States, 49014
      • Pfizer Investigational Site
    • Battle Creek, Michigan, United States, 49017
      • Pfizer Investigational Site
    • Clinton, Michigan, United States, 49236
      • Pfizer Investigational Site
    • Flint, Michigan, United States, 48504
      • Pfizer Investigational Site
    • Muskegon, Michigan, United States, 49444
      • Pfizer Investigational Site
    • Sterling Heights, Michigan, United States, 48310
      • Pfizer Investigational Site
    • Troy, Michigan, United States, 48084
      • Pfizer Investigational Site
    • Warren, Michigan, United States, 48091
      • Pfizer Investigational Site
  • Minnesota
    • Saint Cloud, Minnesota, United States, 56301
      • Pfizer Investigational Site
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Pfizer Investigational Site
  • Nevada
    • Incline Village, Nevada, United States, 89452
      • Pfizer Investigational Site
  • New Jersey
    • Belleville, New Jersey, United States, 07109
      • Pfizer Investigational Site
    • Belvidere, New Jersey, United States, 07823
      • Pfizer Investigational Site
    • Glendora, New Jersey, United States, 08029
      • Pfizer Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Pfizer Investigational Site
  • New York
    • Babylon, New York, United States, 11702
      • Pfizer Investigational Site
    • Brooklyn, New York, United States, 11224
      • Pfizer Investigational Site
    • New Hartford, New York, United States, 13413
      • Pfizer Investigational Site
    • Rochester, New York, United States, 14622
      • Pfizer Investigational Site
    • Williamsville, New York, United States, 14221
      • Pfizer Investigational Site
  • North Carolina
    • Asheboro, North Carolina, United States, 27203
      • Pfizer Investigational Site
    • Charlotte, North Carolina, United States, 28227
      • Pfizer Investigational Site
    • Morehead City, North Carolina, United States, 28557-3126
      • Pfizer Investigational Site
    • Raleigh, North Carolina, United States, 27609
      • Pfizer Investigational Site
    • Raleigh, North Carolina, United States, 27610
      • Pfizer Investigational Site
    • Shelby, North Carolina, United States, 28150
      • Pfizer Investigational Site
    • Tabor City, North Carolina, United States, 28463
      • Pfizer Investigational Site
    • Winston-Salem, North Carolina, United States, 27103
      • Pfizer Investigational Site
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Pfizer Investigational Site
  • Ohio
    • Ashtabula, Ohio, United States, 44004
      • Pfizer Investigational Site
    • Canton, Ohio, United States, 44708
      • Pfizer Investigational Site
    • Cleveland, Ohio, United States, 44113
      • Pfizer Investigational Site
    • Columbus, Ohio, United States, 43207
      • Pfizer Investigational Site
    • Dayton, Ohio, United States, 45419
      • Pfizer Investigational Site
    • McConnelsville, Ohio, United States, 43756
      • Pfizer Investigational Site
    • Zanesville, Ohio, United States, 43701
      • Pfizer Investigational Site
  • Oklahoma
    • Clinton, Oklahoma, United States, 73601
      • Pfizer Investigational Site
  • Oregon
    • Bend, Oregon, United States, 97701
      • Pfizer Investigational Site
  • Pennsylvania
    • Broomall, Pennsylvania, United States, 19008
      • Pfizer Investigational Site
    • Dauphin, Pennsylvania, United States, 17018
      • Pfizer Investigational Site
    • Fogelsville, Pennsylvania, United States, 18051
      • Pfizer Investigational Site
    • Hanover, Pennsylvania, United States, 17331
      • Pfizer Investigational Site
    • Harrisburg, Pennsylvania, United States, 17112
      • Pfizer Investigational Site
    • Jeannette, Pennsylvania, United States, 15644
      • Pfizer Investigational Site
    • Jenkintown, Pennsylvania, United States, 19046
      • Pfizer Investigational Site
    • Jersey Shore, Pennsylvania, United States, 17740
      • Pfizer Investigational Site
    • Norristown, Pennsylvania, United States, 19401
      • Pfizer Investigational Site
    • Philadelphia, Pennsylvania, United States, 19153-2326
      • Pfizer Investigational Site
    • Plymouth Meeting, Pennsylvania, United States, 19462
      • Pfizer Investigational Site
    • Tipton, Pennsylvania, United States, 16684
      • Pfizer Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29412
      • Pfizer Investigational Site
    • Florence, South Carolina, United States, 29501
      • Pfizer Investigational Site
    • Greer, South Carolina, United States, 29651
      • Pfizer Investigational Site
    • North Myrtle Beach, South Carolina, United States, 29582
      • Pfizer Investigational Site
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Pfizer Investigational Site
  • Texas
    • Corpus Christi, Texas, United States, 78414
      • Pfizer Investigational Site
    • Garland, Texas, United States, 75041
      • Pfizer Investigational Site
    • Hurst, Texas, United States, 76054
      • Pfizer Investigational Site
    • Kaufman, Texas, United States, 75142
      • Pfizer Investigational Site
    • Lubbock, Texas, United States, 79410
      • Pfizer Investigational Site
    • Midland, Texas, United States, 79705
      • Pfizer Investigational Site
    • San Antonio, Texas, United States, 78229
      • Pfizer Investigational Site
    • San Marcos, Texas, United States, 78666
      • Pfizer Investigational Site
    • Stephenville, Texas, United States, 76401
      • Pfizer Investigational Site
    • Webster, Texas, United States, 77598
      • Pfizer Investigational Site
  • Utah
    • Layton, Utah, United States, 84041
      • Pfizer Investigational Site
  • Virginia
    • Chesapeake, Virginia, United States, 23320
      • Pfizer Investigational Site
    • Ettrick, Virginia, United States, 23803
      • Pfizer Investigational Site
  • West Virginia
    • Burnsville, West Virginia, United States, 26335
      • Pfizer Investigational Site
    • Charleston, West Virginia, United States, 25314
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Eligible for receiving Exubera treatment based on the approved local label

Exclusion Criteria:

• Pregnant or lactating
• Have a progressive fatal disease or a life expectancy that prohibits them from participating in a five-year research study

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
Experimental: Exubera	Drug: Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes Care; Subjects are randomized to use Exubera. Following initial use of randomized treatment, physicians and subjects are free to change regimens and dosing based on subject response to assigned treatment (as consistent with routine practice). Enrolling physicians are provided with the approved local label for Exubera to guide prescribing and treatment decisions.; Drug: Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes Care; Subjects are randomized to use usual diabetes care. Following initial use of randomized treatment, physicians and subjects are free to change regimens and dosing based on subject response to assigned treatment (as consistent with routine practice).; Other Names: Non-Exubera
Active Comparator: Usual Diabetes Care	Drug: Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes Care; Subjects are randomized to use Exubera. Following initial use of randomized treatment, physicians and subjects are free to change regimens and dosing based on subject response to assigned treatment (as consistent with routine practice). Enrolling physicians are provided with the approved local label for Exubera to guide prescribing and treatment decisions.; Drug: Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes Care; Subjects are randomized to use usual diabetes care. Following initial use of randomized treatment, physicians and subjects are free to change regimens and dosing based on subject response to assigned treatment (as consistent with routine practice).; Other Names: Non-Exubera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Decline in Forced Expiratory Volume (FEV1) Exceeding 20% From Baseline	Persistent decline in FEV1 exceeding 20% from baseline: observed decline in FEV1 exceeding 20% from baseline, 3 months after a confirmed decline (2 consecutive declines within 1 month) in FEV1 exceeding 20% from baseline. Second pulmonary function test (PFT) that confirmed decline was to occur within 14-42 days of the decline. Persistence: PFT that established persistence was to occur within 60-120 days of the confirming (2nd) decline. Index Visit: date subject had final Scheduled spirometry; was to occur within 2 months of Institutional Review Board/Ethics approval of April 2008 amendment.	Baseline, Month 6, Year 1, Year 2, Index Visit
Supplemental Definition of Decline in Forced Expiratory Volume in One Second (FEV1): Number of Subjects	Confirmed FEV1 decline: any two consecutive declines that are >= 14 days apart. The pulmonary function test that established persistence occured >= 60 days after the initial decline. A confirmed decline: any two consecutive declines ≥ 14 days apart. The third PFT that established persistence was to occur ≥ 60 days after the initial decline. Index Visit: date the subject had his/her final scheduled spirometry was to occur within 2 months of Institutional Review Board/Ethics approval of April 2008 amendment.	Baseline, Month 6, Year 1, Year 2, Index Visit
Time to Persistent Decline in FEV1 Exceeding 20% From Baseline	Elapsed time, in days, from the start of subject's participation in the study to the first reading of FEV1 that is: 20% or more below the subject's latest pre-study measurement, subsequently confirmed as a >20% decline [(baseline observed value minus visit observed value)/by baseline observed value *100], and assessed as persistent as defined by protocol process. Censoring time: elapsed time, in days, from the start of a subject's participation in the study to latest valid FEV1 measurement for the particular analysis set of interest. Cox proportional hazards model to estimate treatment effect.	Baseline to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Forced Expiratory Volume in One Second (FEV1)	Change from Baseline: mean of value of observed forced expiratory volume in the first second of forced exhalation [FEV1] in liters [L] at observation minus Baseline value. Index Visit: date subject had final scheduled spirometry; was to occur within 2 months of Institutional Review Board/Ethics approval of April 2008 amendment.	Baseline, Week 26, Week 52, Week 104, Index Visit
Pulmonary Serious Adverse Event (SAE) Composite: SAEs of Asthma, Chronic Obstructive Pulmonary Disease (COPD), Pneumonia, or Acute Bronchitis	Endpoint committee adjudicated the endpoint based on review of medical and hospital records, and results were classified using standard criteria. Definite: definite pneumonia, definite COPD, or definite asthma; possible: possible pneumonia, possible COPD, possible asthma, probable obstructive lung disease not otherwise specified or probable acute bronchitis; definite or possible: either definite or possible; insufficient: insufficient data.	Baseline through End of Study
Time to Event for Pulmonary Serious Adverse Event (SAE) Composite: SAEs of Asthma, Chronic Obstructive Pulmonary Disease (COPD), Pneumonia, or Acute Bronchitis	Elapsed time, in days, from the start of a subject's participation in the study to the date of the first report of an event subsequently confirmed (according to protocol definition) as meeting the criteria for pulmonary SAE composite. Censoring time: elapsed time, in days, from the start of a subject's participation in the study to the latest contact with the subject for the particular analysis set of interest. Cox proportional hazards model to estimate treatment effect.	Baseline to 5 years
All-cause Mortality: Number of Deaths	Endpoint committee adjudicated the endpoint based on review of medical and hospital records, and results were classified using standard criteria (confirmation of deaths by blinded adjudicator(s) through medical records or death certificates). Patients meeting the endpoint All Cause Mortality after adjudication by the endpoint committee.	Baseline through End of Study
Time to Event: All-cause Mortality	Time to all-cause mortality: elapsed time, in days, from the start of a subject's participation in the study to the date of the event subsequently confirmed (according to protocol definition) as meeting the criteria for all-cause mortality. Censoring time: elapsed time, in days, from the start of a subject's participation in the study to the latest contact with the subject for the particular analysis set of interest. Cox proportional hazards model to estimate treatment effect.	Baseline to 5 years
Cardiovascular SAE Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke	Endpoint committee adjudicated based on review of medical/hospital records; results classified using standard criteria. Definite: definite MI or stroke; Possible: possible MI or stroke; Other (non-MI, non-stroke): other cardiovascular event (non-MI, non-stroke); Definite or possible: either definite or possible or both; Insufficient: insufficient data; Death from cardiovascular or cerebrovascular: cardiovascular or cerebrovascular event; Definite or possible or death from cardiovascular or cerebrovascular: either definite or possible or both or cardiovascular or cerebrovascular event.	Baseline through End of Study
Time to Event for Cardiovascular Serious Adverse Event (SAE) Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction, or Non-fatal Stroke	Elapsed time, in days, from the start of a subject's participation in the study to the date of the first event subsequently confirmed (according to protocol definition) as meeting the criteria for cardiovascular SAE composite. Censoring time: elapsed time, in days, from the start of a subject's participation in the study to the latest contact with the subject for the particular analysis set of interest. Cox proportional hazards model to estimate treatment effect.	Baseline to 5 years
Allergic Response Serious Adverse Event (SAE) Composite: SAEs of Anaphylaxis, Angioedema, Generalized Allergic Reaction, or Allergic Bronchospasm	Endpoint committee adjudicated the endpoint based on review of medical and hospital records, and results were classified using standard criteria. Definite or possible: anaphylaxis, angioedema/urticaria, bronchospasm or possible allergic reaction not otherwise specified (NOS); Insufficient: insufficient data.	Baseline through End of Study
Time to Event for Allergic Response Serious Adverse Event (SAE) Composite, Including: SAEs of Anaphylaxis, Angioedema, Generalized Allergic Reaction, or Allergic Bronchospasm	Elapsed time, in days, from the start of a subject's participation in the study to the date of the first event subsequently confirmed (according to protocol definition) as meeting the criteria for allergic response. Censoring time: elapsed time, in days, from the start of a subject's participation in the study to the latest contact with the subject for the particular analysis set of interest. Cox proportional hazards model to estimate treatment effect.	Baseline to 5 years
Change in Glycosylated Hemoglobin (HbA1c) From Baseline	Baseline HbA1c: the latest determination prior to beginning study participation. Change from Baseline: HbA1c at observation (falling within the time window associated with a given analysis set) minus the baseline value.	Baseline, Month 6, Year 1, Year 2, Index Visit
Change in Glycosylated Hemoglobin (HbA1c) From Baseline	Baseline HbA1c taken as the latest determination prior to beginning study participation. Change = on-study value (for measurements falling within the time window associated with a given analysis set) minus the baseline value. Linear model with terms for treatment, baseline HbA1c, time on study, and subject within treatment.	Baseline to 5 years

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Gatto NM, Bracken MB, Kolitsopoulos F, Duggan WT, Koch GG, Wise RA, Jackson NC. Pulmonary and cardiovascular safety of inhaled insulin in routine practice: The Exubera Large Simple Trial (VOLUME). Contemp Clin Trials Commun. 2019 Aug 13;18:100427. doi: 10.1016/j.conctc.2019.100427. eCollection 2020 Jun.
• Kolitsopoulos FM, Gatto NM, Sweetland K, Bracken MB, Jackson N. Implications of product withdrawal on a post-approval pragmatic trial: The VOLUME study experience. Contemp Clin Trials Commun. 2019 Oct 28;16:100477. doi: 10.1016/j.conctc.2019.100477. eCollection 2019 Dec.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: July 31, 2006
• First Submitted That Met QC Criteria: July 31, 2006
• First Posted (Estimate): August 2, 2006

Study Record Updates

• Last Update Posted (Estimate): February 2, 2010
• Last Update Submitted That Met QC Criteria: January 29, 2010
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: Large Simple Trial
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: A2171069