Effect of Roflumilast in Chronic Obstructive Pulmonary Disease (COPD) Patients Treated With Tiotropium: The HELIOS Study (BY217/M2-128) (HELIOS)

This study has been completed.
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ClinicalTrials.gov Identifier:
First received: January 18, 2007
Last updated: May 4, 2012
Last verified: August 2011
The aim of the study is to compare the efficacy of roflumilast to placebo on pulmonary function and symptomatic parameters in patients with chronic obstructive pulmonary disease (COPD) during concomitant administration of tiotropium. The study duration will last up to 28 weeks. The study will provide further data on safety and tolerability of roflumilast.

Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: Roflumilast
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Roflumilast in COPD Patients Treated With Tiotropium. A 24-week, Double-blind Study With 500 µg Roflumilast Once Daily Versus Placebo. The HELIOS Study

Resource links provided by NLM:

Further study details as provided by Takeda:

Primary Outcome Measures:
  • Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1) [ Time Frame: Change from baseline over 24 weeks of treatment ] [ Designated as safety issue: No ]
    Mean change from baseline during the treatment period in pre-bronchodilator FEV1 [L]

Secondary Outcome Measures:
  • Post-bronchodilator FEV1 [ Time Frame: Change from baseline over 24 weeks of treatment ] [ Designated as safety issue: No ]
    Mean change from baseline during the treatment period in post-bronchodilator FEV1 [L]

  • COPD Exacerbation Rate (Moderate or Severe) [ Time Frame: 24 weeks treatment period ] [ Designated as safety issue: No ]

    Mean rate of COPD exacerbations requiring oral or parenteral glucocorticosteroids (=moderate COPD exacerbations), or requiring hospitalization, or leading to death (=severe COPD exacerbations), per patient per year.

    A COPD exacerbation is an event in the natural course of the disease characterized by a change in the patient's baseline dyspnea, cough and/or sputum beyond day-to-day variability sufficient to warrant a change in management [American Thoracic Society (ATS) / European Respiratory Society (ERS) 2005].

  • Transition Dyspnea Index (TDI) Focal Score [ Time Frame: Change from baseline over 24 weeks of treatment ] [ Designated as safety issue: No ]

    The TDI is a recognized questionnaire to measure dyspnea in an out patient COPD population. At baseline, 3 components of dyspnea, each graded with 4 questions, were asked:

    • Functional Impairment
    • Magnitude of Task
    • Magnitude of Effort

    At each of the post-randomization visits questions from the TDI were asked related to 3 components:

    Change in

    • Functional Impairment
    • Magnitude of Task
    • Magnitude of Effort

    Each question in the TDI is graded from -3 (major deterioration) to +3 (major improvement). This results in a TDI Focal Score ranging from -9 to +9.

  • Shortness of Breath Questionnaire (SOBQ) Total Score [ Time Frame: Change from baseline over 24 weeks of treatment ] [ Designated as safety issue: No ]

    Mean change from baseline during the treatment period in SOBQ. This is a 24-item measure that assesses self-reported shortness of breath while performing a variety of activities of daily living.

    The questions were administered at visits V0, V2, V3, V4, V5, V6 and Vend to assess the perceived shortness of breath of the patient.

    For each activity listed in the questionnaire the patient should rate his/her breathlessness on a scale between zero and five, where zero is "not at all breathless" and five is "maximally breathless or too breathless to do the activity".

Enrollment: 743
Study Start Date: January 2007
Study Completion Date: July 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Roflumilast

Roflumilast 500 µg

underlying medication: tiotropium 18 µg, once daily, inhaled

Drug: Roflumilast
500 µg, once daily, oral administration in the morning
Placebo Comparator: Placebo


underlying medication: tiotropium 18 µg, once daily, inhaled

Drug: Placebo
once daily


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

Main Inclusion Criteria:

  • History of COPD for at least 12 months prior to baseline visit and chronic productive cough for 3 months in each of the 2 years prior to baseline visit
  • FEV1/FVC ratio (post-bronchodilator) ≤ 70%
  • FEV1 (post-bronchodilator) between ≥ 40% and ≤ 70% of predicted
  • Treated with tiotropium for at least 3 months before enrollment
  • At least 28 puffs of rescue medication during last week prior to randomization

Main Exclusion Criteria:

  • COPD exacerbation indicated by a treatment with systemic glucocorticosteroids and/or antibiotics not stopped at least 4 weeks prior to baseline visit
  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: NCT00424268

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Sponsors and Collaborators
Principal Investigator: Prof. L M Fabbri University of Modena & Reggio Emilia, Department of Respiratory Diseases, Italy
  More Information

Responsible Party: Nycomed
ClinicalTrials.gov Identifier: NCT00424268     History of Changes
Other Study ID Numbers: BY217/M2-128  2006-004508-37 
Study First Received: January 18, 2007
Results First Received: March 17, 2011
Last Updated: May 4, 2012
Health Authority: Austria: Federal Office for Safety in Health Care
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Italy: The Italian Medicines Agency
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Takeda:

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Tiotropium Bromide
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cholinergic Agents
Cholinergic Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Respiratory System Agents

ClinicalTrials.gov processed this record on May 25, 2016