Pulmonary Disease, Chronic ObstructiveWHISPERNCT02691988
Withdrawal of Inhaled Corticosteroids in Primary Care Patients With COPD
A study testing ICS withdrawal in people with Pulmonary Disease, Chronic Obstructive, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Rationale: Because long-term use of ICS is associated with an increased likelihood of side-effects such as increased risk of pneumonia and loss of bone density, it is important to limit prescription of ICS to patients who have a clear indication for this treatment. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- ICS withdrawal
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 620 participants
- Where
- 1 siteNetherlands
- Study dates
- Dec 2015to Jun 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- COPD diagnosis in the medical record (ICPC code R95 or R91);
- Most recent spirometry result is less than three years old and shows a ratio of the Forced Expiratory Volume in 1 second (FEV1) to the Forced Vital Capacity (FVC) of less than 0.7, in short: FEV1/FVC ratio <0.7 (If no recent spirometry results are available, the patient will be scheduled for a diagnostic spirometric test);
- ICS treatment for at least the past 6 months;
- Accessible electronic medical record and prescription data history of at least one year;
- The subject's COPD is primarily managed by the general practioner (GP) (i.e., not by a chest physician); or if a subject's COPD is treated by a chest physician as well, the chest physician agrees with the invitation of the subject.
- Willing to provide written informed consent;
- Mentally competent.
Who cannot join
- A spirometry test that has demonstrated airflow reversibility (i.e., post-bd FEV1 improvement of at least 12% and 200 ml compared to baseline and/or post-bd FEV1 improvement of 9% of the baseline FEV1 % predicted value) that preceded the initiation of ICS treatment;
- Diagnosis of asthma in the medical record (ICPC code R96);
- Allergic respiratory disease which has been confirmed by a positive skin prick test or specific immunoglobulin E (IgE) in serum as documented in the medical record, in combination with a documented history respiratory allergic symptoms;
- Two or more exacerbations in the previous 12 months that were treated with oral corticosteroids, antibiotics, or both; and/or required a visit to an emergency care facility or hospital admission;
- Use of oral corticosteroids on a regular basis (i.e., more than six weeks in the previous half year) for any reason;
- Currently participating in another intervention study that interferes with the current study;
Show all 9Show fewer
- Has one or more serious other diseases that are likely to lead to study drop-out (e.g., diseases with limited life expectancy) or influence the study results; or
- Pregnancy or women who are trying to conceive a child;
- Unable to read or understand the Dutch language.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Radboud University Medical Centre, Department of Primary and Community Care
Nijmegen, 6500 HB
Tjard R Schermer, PhD, +31 24 3614611, tjard.schermer@radboudumc.nl
Lisette van den Bemt, PhD, +31 24 3619588, lisette.vandenbemt@radboudumc.nl
About this study
Official title: Withdrawal of Inhaled Corticosteroids and the Possible Effect on Exacerbation Rate in Primary Care Patients With COPD
Rationale: Because long-term use of ICS is associated with an increased likelihood of side-effects such as increased risk of pneumonia and loss of bone density, it is important to limit prescription of ICS to patients who have a clear indication for this treatment. In addition, avoiding unnecessary treatment with ICS could reduce the burden that chronic obstructive pulmonary disease (COPD) puts on healthcare budgets. The recently updated COPD guideline of the Dutch college of General Practitioners (NHG) emphasizes the importance of optimizing medical treatment for COPD patients with only limited room for the use of inhaled corticosteroids.
Objective: The objective of the study is to investigate whether discontinuation of inhaled corticosteroids (ICS) for patients without a clear indication for ICS according to current guidelines results in a reduction of ICS use without adverse health effects for the patients involved.
Read more
Study design: The study is a pragmatic, clustered, parallel group, non-inferiority trial in Dutch general practices with a follow-up of 26 weeks per patient.
Study population: 620 COPD patients with confirmed chronic airflow obstruction, aged ≥ 40 yrs who use ICS for at least the prior 6 months without a clear indication.
Intervention (if applicable): Guided ICS withdrawal in optimised COPD management. All study participants (of both study arms) will receive recommendations on optimal bronchodilator therapy and a personalized action plan to recognize symptom deterioration in an early stage.
Main study parameters/endpoints: Number of exacerbation-free weeks. Secondary study parameters: successful cessation of ICS, time to first exacerbation, number of moderate and severe exacerbations, health-related quality of life, health status, and pneumonias. Moreover, information on the process of care and costs will be collected.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Many COPD patients use ICS without a clear indication. Long-term use of ICS is associated with an increased likelihood of side-effects such as increased risk of pneumonia and loss of bone density and should be avoided in those who do not benefit from it. However, there is a small subgroup of COPD patients that have reduced numbers of exacerbations because of their ICS use and it is impossible to identify a priori the patients who this applies too. Therefore, it is important that the ICS discontinuation is guided to detect potential deteriorations early on.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- ICS withdrawal, Usual care
- Keywords
- Inhaled corticosteroids, General practice, Primary care, Pharmacotherapy
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ICS withdrawalOther
Bronchodilator therapy is optimized according to the latest COPD guideline of the Dutch College of General Practitioners (NHG) and inhaled corticosteroids are withdrawn.
Usual careOther
Bronchodilator therapy is optimized according to the latest COPD guideline of the Dutch College of General Practitioners (NHG)
| Study group | Role | What they receive |
|---|---|---|
| ICS withdrawal | Experimental | Guided ICS withdrawal combined with optimization of bronchodilator treatment Receives: Other: ICS withdrawal |
| Usual care | Active comparator | Optimization of bronchodilator treatment Receives: Other: Usual care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of exacerbation-free weeks (EFWs)
Weeks in which the patient does not experience a worsening of his respiratory condition according to accepted symptom-based definitions of an exacerbation. This outcome is measured on a weekly basis with the Telephonic Exacerbation Assessment System (TEXAS)
Measured: 6 months
Secondary outcomes (7)
Successful ICS withdrawal
The proportion of patients with successful cessation of ICS, i.e. a period of 26 weeks after the withdrawal date without the occurrence of a moderate or severe exacerbation or reintroduction of ICS treatment.
Measured: 6 months
Time to first exacerbation
Time (in weeks) to first exacerbation will be calculated for all subjects. The definition for an exacerbation will be comparable to the definition used for EFWs. Information on time to first exacerbation will be collected using TEXAS.
Measured: Max. 6 months
Moderate and severe exacerbations
A moderate exacerbation is defined as prescription of a course of oral corticosteroids and/or antibiotics related to deterioration of COPD registered as episodes in the electronic patient record. A severe exacerbation is defined as a COPD-related ER visit and/or unscheduled COPD-related hospital admission.
Measured: 6 months
Health status (CCQ)
Health status will be measured using the Clinical COPD Questionnaire (CCQ) which has been developed as a COPD specific health status measurement. CCQ questionnaires that are filled out at the start (t=0) and end of the study period (t = 26 weeks) will be used to evaluate the difference in change in CCQ score between the intervention and control groups.
Measured: 6 months
Health-related quality of life (HRQoL)
Disease specific HRQoL will be assessed with the Short-form Chronic Respiratory Questionnaire (SF-CRQ) at baseline and 26 weeks of follow up.
Measured: 6 months
General health state (EQ-5D-3L)
The EuroQol-5 Dimensions-3 Levels (EQ-5D-3L) will be used to assess the general health state of subjects at the start and after 26 weeks.
Measured: 6 months
Side effects of inhaled corticosteroids
Side effects of inhaled corticosteroids will be measured using the Inhaled Corticosteroids Questionnaire Short form (ICQ-S).
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2016 (estimated)
- Study startDec 2015
- Primary completionJan 2017 (estimated)
- Study completionJun 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 620 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis, Boehringer Ingelheim
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02691988
- Sponsor's protocol ID
- NL52880.091.15
- Acronym
- WHISPER
- Status last verified
- Feb 2016
- First submitted
- 22 Feb 2016
- Last updated
- 25 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Withdrawal of Inhaled Corticosteroids and the Possible Effect on Exacerbation Rate in Primary Care Patients With COPD
- ClinicalTrials.gov ID
- NCT02691988
- Acronym / sponsor ID
- WHISPER / NL52880.091.15
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Keywords
- Inhaled corticosteroids, General practice, Primary care, Pharmacotherapy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 620 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Novartis, Boehringer Ingelheim
- Study start
- Dec 2015
- Primary completion
- Jan 2017 (estimated)
- Study completion
- Jun 2017 (estimated)
- First posted
- 25 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Rationale: Because long-term use of ICS is associated with an increased likelihood of side-effects such as increased risk of pneumonia and loss of bone density, it is important to limit prescription of ICS to patients who have a clear indication for this treatment. In addition, avoiding unnecessary treatment with ICS could reduce the burden that chronic obstructive pulmonary disease (COPD) puts on healthcare budgets. The recently updated COPD guideline of the Dutch college of General Practitioners (NHG) emphasizes the importance of optimizing medical treatment for COPD patients with only limited room for the use of inhaled corticosteroids.
Objective: The objective of the study is to investigate whether discontinuation of inhaled corticosteroids (ICS) for patients without a clear indication for ICS according to current guidelines results in a reduction of ICS use without adverse health effects for the patients involved.
Study design: The study is a pragmatic, clustered, parallel group, non-inferiority trial in Dutch general practices with a follow-up of 26 weeks per patient.
Study population: 620 COPD patients with confirmed chronic airflow obstruction, aged ≥ 40 yrs who use ICS for at least the prior 6 months without a clear indication.
Intervention (if applicable): Guided ICS withdrawal in optimised COPD management. All study participants (of both study arms) will receive recommendations on optimal bronchodilator therapy and a personalized action plan to recognize symptom deterioration in an early stage.
Main study parameters/endpoints: Number of exacerbation-free weeks. Secondary study parameters: successful cessation of ICS, time to first exacerbation, number of moderate and severe exacerbations, health-related quality of life, health status, and pneumonias. Moreover, information on the process of care and costs will be collected.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Many COPD patients use ICS without a clear indication. Long-term use of ICS is associated with an increased likelihood of side-effects such as increased risk of pneumonia and loss of bone density and should be avoided in those who do not benefit from it. However, there is a small subgroup of COPD patients that have reduced numbers of exacerbations because of their ICS use and it is impossible to identify a priori the patients who this applies too. Therefore, it is important that the ICS discontinuation is guided to detect potential deteriorations early on.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ICS withdrawal | Experimental | Other: ICS withdrawalGuided ICS withdrawal combined with optimization of bronchodilator treatment |
| Usual care | Active comparator | Other: Usual careOptimization of bronchodilator treatment |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- COPD diagnosis in the medical record (ICPC code R95 or R91);
- Most recent spirometry result is less than three years old and shows a ratio of the Forced Expiratory Volume in 1 second (FEV1) to the Forced Vital Capacity (FVC) of less than 0.7, in short: FEV1/FVC ratio <0.7 (If no recent spirometry results are available, the patient will be scheduled for a diagnostic spirometric test);
- ICS treatment for at least the past 6 months;
- Accessible electronic medical record and prescription data history of at least one year;
- The subject's COPD is primarily managed by the general practioner (GP) (i.e., not by a chest physician); or if a subject's COPD is treated by a chest physician as well, the chest physician agrees with the invitation of the subject.
Key exclusion criteria (9 listed)
- A spirometry test that has demonstrated airflow reversibility (i.e., post-bd FEV1 improvement of at least 12% and 200 ml compared to baseline and/or post-bd FEV1 improvement of 9% of the baseline FEV1 % predicted value) that preceded the initiation of ICS treatment;
- Diagnosis of asthma in the medical record (ICPC code R96);
- Allergic respiratory disease which has been confirmed by a positive skin prick test or specific immunoglobulin E (IgE) in serum as documented in the medical record, in combination with a documented history respiratory allergic symptoms;
- Two or more exacerbations in the previous 12 months that were treated with oral corticosteroids, antibiotics, or both; and/or required a visit to an emergency care facility or hospital admission;
- Use of oral corticosteroids on a regular basis (i.e., more than six weeks in the previous half year) for any reason;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ICS withdrawalBronchodilator therapy is optimized according to the latest COPD guideline of the Dutch College of General Practitioners (NHG) and inhaled corticosteroids are withdrawn. | Other | ICS withdrawal |
| Usual careBronchodilator therapy is optimized according to the latest COPD guideline of the Dutch College of General Practitioners (NHG) | Other | Usual care |
Primary outcome
Number of exacerbation-free weeks (EFWs)
Time frame: 6 months
Weeks in which the patient does not experience a worsening of his respiratory condition according to accepted symptom-based definitions of an exacerbation. This outcome is measured on a weekly basis with the Telephonic Exacerbation Assessment System (TEXAS)
7 secondary outcomes
Successful ICS withdrawal
Time frame: 6 months
Time to first exacerbation
Time frame: Max. 6 months
Moderate and severe exacerbations
Time frame: 6 months
Health status (CCQ)
Time frame: 6 months
Health-related quality of life (HRQoL)
Time frame: 6 months
General health state (EQ-5D-3L)
Time frame: 6 months
Side effects of inhaled corticosteroids
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ICS withdrawal in people with Pulmonary Disease, Chronic Obstructive, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tjard R Schermer, PhD (0031243614611, Tjard.Schermer@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of exacerbation-free weeks (EFWs) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2016.