Evaluation of Tiotropium 5 µg/Day Delivered Via the Respimat® Inhaler Over 48 Weeks in Patients With Severe Persistent Asthma on Top of Usual Care (Study II)

NCT ID: NCT00776984

Last Updated: 2014-09-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 453 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31

Brief Summary

The trial is a randomised, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of 5 µg tiotropium over a 48-week treatment period as compared to placebo. Tiotropium inhalation solution delivered by the Respimat® inhaler will be examined as add-on controller therapy on top of usual care in patients with severe persistent asthma. The primary objective of each trial is to evaluate the long term efficacy of tiotropium over placebo on top of usual care in patients with severe persistent asthma as determined by pulmonary function testing, effects on asthma exacerbations, effects on quality of life, on asthma control and health care resource utilisation. The secondary objective of each trial is to compare the long term safety of tiotropium with placebo in this patient population.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

tiotropium 5mcg/day

patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution

Group Type: EXPERIMENTAL

tiotropium 5mcg/day

Intervention Type: DRUG

Intervention = Randomisation: patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution

placebo

patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution

Group Type: EXPERIMENTAL

placebo

Intervention Type: DRUG

Intervention = Randomisation: patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution

Interventions

tiotropium 5mcg/day

Intervention = Randomisation: patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution

Intervention Type: DRUG

placebo

Intervention = Randomisation: patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. All patients must sign and date an Informed Consent Form consistent with ICH-GCP guidelines and local legislation prior to participation in the trial (i.e. prior to any trial procedures, including any pre-trial washout of medications and medication restrictions for pulmonary function test at Visit 1).

2. Male or female patients aged at least 18 years but not more than 75 years.

3. All patients must have at least a 5-year history of asthma at the time of enrolment into the trial and the diagnosis of asthma must have been made before the patient´s age of 40.

4. All patients must have a diagnosis of severe persistent asthma and must be symptomatic despite treatment with high, stable doses of inhaled corticosteroids and a long-acting beta adrenergic agent

5. All patients must have a history of one or more asthma exacerbation in the past year.

6. Patients must have evidence of treated, severe, persistent asthma in postbronchodilator pulmonary function tests.

7. Patients should be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment and who have a smoking history of less than 10 pack years

8. Patients must be able to use the Respimat® inhaler correctly

9. Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of the electronic diary/peak flow meter.

Exclusion Criteria

1. Patients with a significant disease other than asthma. A significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the trial, or (ii) influence the results of the trial, or (iii) cause concern regarding the patient´s ability to participate in the trial.

2. Patients with clinically relevant abnormal screening haematology or blood chemistry.

3. Patients with a recent history (i.e. six months or less) of myocardial infarction, hospitalisation for cardiac failure during the past year, any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year, known active tuberculosis, malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years (treated basal cell carcinoma allowed), lung diseases other than asthma (e.g. COPD), significant alcohol or drug abuse within the past two years, patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1.

4. Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the 6 weeks prior to the screening visit (Visit 1).

5. Patients using oral corticosteroid medication at stable doses exceeding 5 mg prednisolone or prednisolone equivalent every day or 10 mg prednisolone or prednisolone equivalent every second day.

6. Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the tiotropium inhalation solution.

7. Pregnant or nursing women or women of childbearing potential not using a highly effective method of birth control. Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation/salpingectomy, or post-menopausal for at least two years.

8. Patients who have taken an investigational drug within four weeks or six half-lives (whichever is greater) prior to Visit 1.

9. Patients who have been treated with the long-acting anticholinergic tiotropium (Spiriva®), beta-blocker medication, oral beta-adrenergics, other non-approved and according to international guidelines not recommended ´experimental´ drugs for routine asthma therapy (e.g. TNF-alpha blockers, methotrexate, cyclosporin) within four weeks prior to the Screening Visit (Visit 1) or during the screening period.

10. Patients with any asthma exacerbation or respiratory tract infection in the four weeks prior to the trial.

11. Patients who have previously been randomised in this trial or in the respective twin trial (205.416 versus 205.417) or are currently participating in another trial.

12. Patients with a known narrow-angle glaucoma.

Note:

As with other anticholinergic drugs, tiotropium should be used with caution in patients with prostatic hyperplasia or bladder neck obstruction.

As with all predominantly renally excreted drugs, patients with moderate to severe renal impairment (known creatinine clearance of <= 50 mL/min) treated with tiotropium should be monitored closely.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

205.417.01061 Boehringer Ingelheim Investigational Site

Fountain Valley, California, United States

205.417.01052 Boehringer Ingelheim Investigational Site

Fresno, California, United States

205.417.01051 Boehringer Ingelheim Investigational Site

Stockton, California, United States

205.417.01056 Boehringer Ingelheim Investigational Site

Waterbury, Connecticut, United States

205.417.01065 Boehringer Ingelheim Investigational Site

Pensacola, Florida, United States

205.417.01059 Boehringer Ingelheim Investigational Site

Chicago, Illinois, United States

205.417.01068 Boehringer Ingelheim Investigational Site

Normal, Illinois, United States

205.417.01063 Boehringer Ingelheim Investigational Site

Louisville, Kentucky, United States

205.417.01064 Boehringer Ingelheim Investigational Site

New Orleans, Louisiana, United States

205.417.01066 Boehringer Ingelheim Investigational Site

Omaha, Nebraska, United States

205.417.01069 Boehringer Ingelheim Investigational Site

Ocean City, New Jersey, United States

205.417.01062 Boehringer Ingelheim Investigational Site

Albany, New York, United States

205.417.01058 Boehringer Ingelheim Investigational Site

Great Neck, New York, United States

205.417.01055 Boehringer Ingelheim Investigational Site

Rockville Centre, New York, United States

205.417.01067 Boehringer Ingelheim Investigational Site

High Point, North Carolina, United States

205.417.01070 Boehringer Ingelheim Investigational Site

Canton, Ohio, United States

205.417.01053 Boehringer Ingelheim Investigational Site

Upland, Pennsylvania, United States

205.417.01054 Boehringer Ingelheim Investigational Site

Richmond, Virginia, United States

205.417.61051 Boehringer Ingelheim Investigational Site

Concord, New South Wales, Australia

205.417.02051 Boehringer Ingelheim Investigational Site

Mississauga, Ontario, Canada

205.417.02053 Boehringer Ingelheim Investigational Site

Ottawa, Ontario, Canada

205.417.02052 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

205.417.45052 Boehringer Ingelheim Investigational Site

Aalborg, , Denmark

205.417.45051 Boehringer Ingelheim Investigational Site

Aarhus C, , Denmark

205.417.49052 Boehringer Ingelheim Investigational Site

Berlin, , Germany

205.417.49054 Boehringer Ingelheim Investigational Site

Hamburg, , Germany

205.417.49053 Boehringer Ingelheim Investigational Site

Lübeck, , Germany

205.417.49051 Boehringer Ingelheim Investigational Site

Rüdersdorf, , Germany

205.417.49055 Boehringer Ingelheim Investigational Site

Weinheim, , Germany

205.417.39052 Boehringer Ingelheim Investigational Site

Bussolengo (vr), , Italy

205.417.39054 Boehringer Ingelheim Investigational Site

Milan, , Italy

205.417.39051 Boehringer Ingelheim Investigational Site

Pavia, , Italy

205.417.39053 Boehringer Ingelheim Investigational Site

Pietra Ligure (sv), , Italy

205.417.81063 Boehringer Ingelheim Investigational Site

Himeji, Hyogo, , Japan

205.417.81056 Boehringer Ingelheim Investigational Site

Hiroshima, Hiroshima, , Japan

205.417.81051 Boehringer Ingelheim Investigational Site

Itabashi-ku, Tokyo, , Japan

205.417.81059 Boehringer Ingelheim Investigational Site

Kagoshima, Kagoshima, , Japan

205.417.81053 Boehringer Ingelheim Investigational Site

Kishiwada, Osaka, , Japan

205.417.81057 Boehringer Ingelheim Investigational Site

Kitakyusyu, Fukuoka, , Japan

205.417.81058 Boehringer Ingelheim Investigational Site

Koga, Fukuoka, , Japan

205.417.81055 Boehringer Ingelheim Investigational Site

Kurashiki, Okayama, , Japan

205.417.81064 Boehringer Ingelheim Investigational Site

Kurume, Fukuoka, , Japan

205.417.81062 Boehringer Ingelheim Investigational Site

Morioka, Iwate, , Japan

205.417.81052 Boehringer Ingelheim Investigational Site

Osaka-sayama, Osaka, , Japan

205.417.81066 Boehringer Ingelheim Investigational Site

Sendai, Miyagi, , Japan

205.417.81065 Boehringer Ingelheim Investigational Site

Seto, Aichi, , Japan

205.417.81060 Boehringer Ingelheim Investigational Site

Urasoe, Okinawa, , Japan

205.417.81061 Boehringer Ingelheim Investigational Site

Urasoe, Okinawa, , Japan

205.417.81054 Boehringer Ingelheim Investigational Site

Wakayama, Wakayama, , Japan

205.417.31051 Boehringer Ingelheim Investigational Site

Groningen, , Netherlands

205.417.31053 Boehringer Ingelheim Investigational Site

Leeuwarden, , Netherlands

205.417.31052 Boehringer Ingelheim Investigational Site

Schiedam, , Netherlands

205.417.64054 Boehringer Ingelheim Investigational Site

Auckland NZ, , New Zealand

205.417.64053 Boehringer Ingelheim Investigational Site

Christchurch, , New Zealand

205.417.64052 Boehringer Ingelheim Investigational Site

Newtown Wellington NZ, , New Zealand

205.417.64051 Boehringer Ingelheim Investigational Site

Tauranga, , New Zealand

205.417.07051 Boehringer Ingelheim Investigational Site

Saint Petersburg, , Russia

205.417.07052 Boehringer Ingelheim Investigational Site

Saint Petersburg, , Russia

205.417.07053 Boehringer Ingelheim Investigational Site

Saint Petersburg, , Russia

205.417.38153 Boehringer Ingelheim Investigational Site

Belgrade, , Serbia

205.417.38152 Boehringer Ingelheim Investigational Site

Kamenitz, , Serbia

205.417.38151 Boehringer Ingelheim Investigational Site

Niš, , Serbia

205.417.27051 Boehringer Ingelheim Investigational Site

Bellville, , South Africa

205.417.27052 Boehringer Ingelheim Investigational Site

Cape Town, , South Africa

205.417.27053 Boehringer Ingelheim Investigational Site

Cape Town, , South Africa

205.417.27054 Boehringer Ingelheim Investigational Site

Cape Town, , South Africa

205.417.90052 Boehringer Ingelheim Investigational Site

Ankara, , Turkey (Türkiye)

205.417.90053 Boehringer Ingelheim Investigational Site

Ankara, , Turkey (Türkiye)

205.417.90051 Boehringer Ingelheim Investigational Site

İzmit, , Turkey (Türkiye)

205.417.38053 Boehringer Ingelheim Investigational Site

Kharkiv, , Ukraine

205.417.38051 Boehringer Ingelheim Investigational Site

Kiev, , Ukraine

205.417.38052 Boehringer Ingelheim Investigational Site

Vinnytsia, , Ukraine

205.417.44051 Boehringer Ingelheim Investigational Site

Chertsey, , United Kingdom

205.417.44053 Boehringer Ingelheim Investigational Site

Exeter, , United Kingdom

205.417.44052 Boehringer Ingelheim Investigational Site

Windsor, , United Kingdom

Countries

United States; Australia; Canada; Denmark; Germany; Italy; Japan; Netherlands; New Zealand; Russia; Serbia; South Africa; Turkey (Türkiye); Ukraine; United Kingdom

References

Oba Y, Anwer S, Maduke T, Patel T, Dias S. Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022 Dec 6;12(12):CD013799. doi: 10.1002/14651858.CD013799.pub2.

Reference Type: DERIVED

PMID: 36472162 (View on PubMed)

Halpin DMG, Meltzer EO, Pisternick-Ruf W, Moroni-Zentgraf P, Engel M, Zaremba-Pechmann L, Casale T, FitzGerald JM. Peak expiratory flow as an endpoint for clinical trials in asthma: a comparison with FEV1. Respir Res. 2019 Jul 18;20(1):159. doi: 10.1186/s12931-019-1119-6.

Reference Type: DERIVED

PMID: 31319851 (View on PubMed)

Casale TB, Bateman ED, Vandewalker M, Virchow JC, Schmidt H, Engel M, Moroni-Zentgraf P, Kerstjens HAM. Tiotropium Respimat Add-on Is Efficacious in Symptomatic Asthma, Independent of T2 Phenotype. J Allergy Clin Immunol Pract. 2018 May-Jun;6(3):923-935.e9. doi: 10.1016/j.jaip.2017.08.037. Epub 2017 Nov 22.

Reference Type: DERIVED

PMID: 29174062 (View on PubMed)

Kerstjens HA, Engel M, Dahl R, Paggiaro P, Beck E, Vandewalker M, Sigmund R, Seibold W, Moroni-Zentgraf P, Bateman ED. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012 Sep 27;367(13):1198-207. doi: 10.1056/NEJMoa1208606. Epub 2012 Sep 2.

Reference Type: DERIVED

PMID: 22938706 (View on PubMed)

Other Identifiers

2008-001414-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

205.417

Identifier Type: -

Identifier Source: org_study_id