12 Week Efficacy of Tiotropium Versus Placebo in Patients With Mild COPD According to Swedish Guidelines (SPIRIMILD)

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00144196
First received: September 2, 2005
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

To show that treatment with tiotropium inhalation capsules (18 μg q.d.) via HandiHaler® improves lung function in patients with mild COPD according to Swedish guidelines.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: tiotropium (Spiriva)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A 12-week Double-blind, Randomised, Parallel-group, Multi-centre Study Evaluating the Efficacy of Tiotropium Versus Placebo in Patients With Mild COPD, According to Swedish Guidelines (SPIRIMILD)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • The primary efficacy endpoint is defined as area under the curve of change in FEV1 from baseline for the time period from pre-dose to 2 hours post dose (AUC0 2hFEV1) after 12 weeks of randomised treatment. [ Time Frame: week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in trough FEV1 from baseline after 12 weeks of randomized treatment [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • Change in trough FEV1 % of predicted after 12 weeks of randomized treatment [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • AUC0-2h (FEV1 % of predicted) after 12 weeks of randomized treatment [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • Change in trough forced vital capacity (FVC) from baseline after 12 weeks of randomized treatment [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • AUC0-2hFVC after 12 weeks of randomized treatment [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • Weekly average number of doses of rescue therapy used in the daytime, at nighttime, and total daily [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • Change in Baseline Dyspnea Index (BDI) scores (R96-2117) [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • Change in health related quality of life (HRQoL) scores according to EQ 5D (R96-2382) [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • Change of symptom score according to Medical Research Council (MRC) scale [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • Change in smoking status [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • Change in working status [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • Incidences of adverse events [ Time Frame: week 2, 12 ] [ Designated as safety issue: No ]
  • Pulse rate measured just before spirometry [ Time Frame: week 2, 12 ] [ Designated as safety issue: No ]
  • systolic blood pressure, measured just before spirometry [ Time Frame: week 2, 12 ] [ Designated as safety issue: No ]
  • diastolic blood pressure, measured just before spirometry [ Time Frame: week 2, 12 ] [ Designated as safety issue: No ]

Estimated Enrollment: 224
Study Start Date: March 2004
Estimated Study Completion Date: July 2005
Primary Completion Date: July 2005 (Final data collection date for primary outcome measure)
Detailed Description:

Following an initial screening at the screening visit(Visit 1), patients enter a 2 week run-in period. Patients are allowed to take salbutamol (Ventoline, Diskus, 0.2 mg) prn as rescue medication and have to record their daily use of it on the Patient's Diary. Patients who meet all inclusion and none of the exclusion criteria at the check at Visit 2 will be randomised thereafter into the randomised treatment period of the study during which they will receive either tiotropium(Spiriva) or placebo in blinded fashion.

On Day 0 (Visit 2), the first administration of blinded study medication (tiotropium(Spiriva) or matching placebo) will be performed at the study site, after a pre-dose pulmonary function test (PFT) has been carried out. First administration of blinded study medication will be monitored by the investigator. Post dose PFTs will be performed at 30 min, 1 and 2 hours.

On Days 1 to 83 except Day 14, the blinded study medication will be self-administered by the patients at home. The patients will inhale one capsule (tiotropium)(Spiriva) or matching placebo) using the HandiHaler device once daily in the morning. The morning dose of the blinded study medication should be taken at approximately the same time each morning between 7:00 a.m. and 10:00 a.m.

At visit 3 and 4 PFTs will be performed predose and post dose at 30 minutes, 1 and 2 hours

Study Hypothesis:

The rationale of the study is to show that treatment with tiotropium (Spiriva) 18 ?g inhalation capsule via HandiHaler once daily improves FEV1 when compared with placebo in patients with mild COPD according to Swedish guidelines, i.e., a post-bronchodilator FEV1 < 60% of predicted normal and FEV1 < 70% of FVC.

Comparison(s):

One group will be treated with inhalation powder capsules of tiotropium (Spiriva), 18 micrograms once daily. The other group will be treated with matching placebo. Randomisation is 1:1

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients who have signed an written informed consent consistent with ICH GCP guidelines and local legislations prior to participation in the trial.
  2. Patients with a diagnosis of COPD. COPD is defined as a disease state characterised by the presence of airflow obstruction often due to chronic bronchitis or emphysema; the airflow obstruction is generally progressive, may be accompanied by airway hyperreactivity, and may be partially reversible.
  3. Patients 40 years of age or older without any restriction to sex.
  4. Patients who currently smoke or who are ex-smokers with a cigarette smoking history of >10 pack-years.
  5. Patients who have a relatively stable airway obstruction (at least 4 weeks free of COPD exacerbations) with a post bronchodilator FEV1 ? 60% of predicted normal, a post bronchodilation FEV1 < 70% of FVC, and a MRC symptom score minimum of 2 at Visit 1

Exclusion Criteria:

  1. Patients with a history of asthma, allergic rhinitis, atopy, or who have a total (absolute) blood eosinophil count ? 600 per mm3 (= 0.6 * 109/L) of the first determination at Visit 1
  2. Patients with known moderate or severe renal insufficiency.
  3. Patients with a recent history (i.e., 6 months or less prior to Visit 1) of myocardial infarction.
  4. Patients with any unstable or life threatening cardiac arrhythmia, including patients with a newly diagnosed, clinically relevant arrhythmia on the electrocardiogram (ECG) performed at Visit 1 as well as patients with cardiac arrhythmia requiring an intervention (i.e., hospitalisation, cardioversion, pacemaker placement, and automatic implantable cardiac defibrillator (AICD) placement) or a change in drug therapy during the last year prior to Visit 1.
  5. Patients who regularly use oxygen therapy.
  6. Patients with known active tuberculosis.
  7. Patients with a history of cancer within the last 5 years. Patients with treated basal cell carcinoma are allowed.
  8. Patients with a history of life threatening pulmonary obstruction or a history of cystic fibrosis or clinically evident bronchiectasis.
  9. Patients who have undergone thoracotomy with pulmonary resection.
  10. Patients who are currently in a pulmonary rehabilitation program or who have completed a pulmonary rehabilitation program in the 6 weeks prior to the screening visit (Visit 1).
  11. Patients with known hypersensitivity to anticholinergic drugs, lactose or any other components of the inhalation capsule delivery system.
  12. Patients with known symptomatic hyperplasia or bladder neck obstruction. Patients being treated for prostatic hyperplasia and report minimal symptoms may be included and should continue their medications.
  13. Patients with known narrow-angle glaucoma.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00144196

Locations
Sweden
Boehringer Ingelheim Investigational Site
?tvidaberg, Sweden, 597 26
Boehringer Ingelheim Investigational Site
Alvesta, Sweden, 342 36
Boehringer Ingelheim Investigational Site
Boden, Sweden, 961 44
Boehringer Ingelheim Investigational Site
Dalum, Sweden, 520 25
Boehringer Ingelheim Investigational Site
Gislaved, Sweden, 332 30
Boehringer Ingelheim Investigational Site
Goteborg, Sweden, 416 65
Boehringer Ingelheim Investigational Site
Goteborg, Sweden, 411 53
Boehringer Ingelheim Investigational Site
Hasselby, Sweden, 165 55
Boehringer Ingelheim Investigational Site
Helsingborg, Sweden, 254 67
Boehringer Ingelheim Investigational Site
Helsingborg, Sweden, 254 43
Boehringer Ingelheim Investigational Site
Hollviken, Sweden, 236 51
Jakobsbergs sjukhus, Birgittavagen 4
Jarfalla, Sweden, 17731
Boehringer Ingelheim Investigational Site
Kalmar, Sweden, 393 50
Boehringer Ingelheim Investigational Site
Karlstad, Sweden, 65224
Boehringer Ingelheim Investigational Site
Kristianstad, Sweden, 291 38
Boehringer Ingelheim Investigational Site
Linkoping, Sweden, 581 88
KvartersAkuten, Timmermansgatan 26
Lule?, Sweden, 972 31
Boehringer Ingelheim Investigational Site
Lule?, Sweden, 971 89
Boehringer Ingelheim Investigational Site
Lund, Sweden, 221 85
Boehringer Ingelheim Investigational Site
Motala, Sweden, 591 36
Boehringer Ingelheim Investigational Site
Skarholmen, Sweden, 127 37
Boehringer Ingelheim Investigational Site
Stockholm, Sweden, 114 86
Halsocentralen, Hans?kervagen 1A
Stugun, Sweden, 830 76
Alno V?rdcentral, Raholmsvagen 24
Sundsvall, Sweden, 865 31
Boehringer Ingelheim Investigational Site
Sunne, Sweden, 686 22
Boehringer Ingelheim Investigational Site
Ulricehamn, Sweden, 523 26
Boehringer Ingelheim Investigational Site
Uppsala, Sweden, 754 27
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Study Coordinator B.I. Sweden AB
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00144196     History of Changes
Other Study ID Numbers: 205.281
Study First Received: September 2, 2005
Last Updated: July 22, 2014
Health Authority: Sweden: Medical Products Agency

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases
Lung Diseases, Obstructive
Tiotropium
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014