AsthmaPhase 4EVITANCT02424552
Effect of Vitamin D as add-on Therapy for Vitamin D Insufficient Patients With Severe Asthma
A Phase 4 study testing Vitamin D3 in people with Asthma, run by Johannes Gutenberg University Mainz at 9 sites in Germany.
Trial summary
The purpose of the EVITA trial is to compare the effects of vitamin D therapy with placebo on reducing the dose of inhaled or oral corticosteroids in patients with severe asthma and vitamin D insufficiency. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Asthma
- What is being tested?
- Vitamin D3
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 9 sitesGermany
- Study dates
- 26 Jun 2015to 9 Mar 2017
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients, age ≥ 18 years
- A pulmonary specialist documented diagnosis of severe asthma according to the Global Initiative for Asthma and the German Asthma Network (GAN, www.german-asthma-net.de)
- Treatment with long-acting β2-agonists (LABA) and inhaled corticosteroids (ICS) at a dose of at least 1000 µg beclomethasone (or equivalent) per day, - chronic oral corticosteroid (OCS) use is allowed Stable asthma medication for ≥1 month prior to screening (≥4 months for omalizumab)
- Asthma Control Questionnaire (ACQ-5) score ≥ 1.5
- Vitamin D insufficiency as defined by a serum vitamin D concentration of < 30 ng/ml but ≥ 10 ng/ml at screening
Who cannot join
- Patients on vitamin D substitution
- Current smokers or ex-smokers with a smoking history of more than 10 pack-years
- Pregnant or nursing women or women who intend to become pregnant during the study
- Known impaired renal function (GFR < 30 ml/min) and history of physician-diagnosed nephrolithiasis
- Use of other investigational drugs during the study or within 30 days of screening
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Germany9 sites
Pneumologische Gemeinschaftspraxis Dr. Rolke & Dr. Rückert
Aschaffenburg, D-63739
Medizinische Klinik III für Pneumologie, allergologie, Schlaf- und Beatmungsmedizin, Berufsgenossenschaftliches Universitätsklinikum Bochum-Bergmannsheil GmbH
Bochum, D-44789
IKF Pneumologie GmbH & Co.KG
Frankfurt, D-60596
Pneumologisches Forschungsinstitut der LungenClinic Grosshansdorf
Großhansdorf, D-22927
Studienzentrum KPPK GmbH
Koblenz, D-56068
KLB - Gesundheitsforschung Lübeck GmbH
Lübeck, D-23552
Pneumologie, III. Medizinische Klinik, Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, D-55131
Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin II/Pneumologie
Regensburg, D-93053
Lungenpraxis Schleswig
Schleswig, D-24837
About this study
Official title: EVITA Trial: Effect of VItamin D as add-on Therapy for Vitamin D Insufficient Patients With Severe Asthma: a Randomized, Double-blind, Placebo-controlled Trial
The purpose of the EVITA trial is to compare the effects of vitamin D therapy with placebo on reducing the dose of inhaled or oral corticosteroids in patients with severe asthma and vitamin D insufficiency.
Read the detailed description
Patients with severe asthma represent the greatest unmet medical need among the asthmatic population, in particular due to their high risk of severe exacerbations. A substantial proportion of these patients does not achieve asthma control despite even high-dose ICS and LABA treatment, necessitating add-on therapy. For these patients oral corticosteroids (OCS) are a preferred treatment modality, which will inevitably lead to severe side effects. A high Proportion of patients with severe Asthma are Vitamin D insufficient (< 30 ng/ml). It is therefore tempting to speculate that vitamin D substitution in vitamin D insufficient patients who continue to experience suboptimal asthma control on ICS and LABA or ICS/LABA plus OCS treatment may boost corticosteroid responsiveness, thereby potentially reducing corticosteroid dose requirements and improving key parameters of asthma control.
The present study is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of treatment with vitamin D at a dose of 4000 IU/day administered daily following a single loading dose of 100 000 IU upon study entry over a period of 24 weeks in patients with severe asthma and vitamin D insufficiency. During the study, all patients will remain on their existing maintenance asthma therapy throughout the study, in addition to the study treatment, while reducing inhaled or oral steroids according to study protocol. The study consists of a 2-week run-in period, a 24 week double-blind treatment period including a 12 week steroid stable phase and two steroid reduction phases, followed by a follow-up visit 4 weeks after last study medication intake. The active treatment arm in this study will be standard of care plus vitamin D (loading dose of 100 000 IU upon study entry, to be followed by 4000 IU/day for the rest of the study period) while the comparator arm will be standard of care plus placebo.
- Conditions
- Asthma
- Being tested
- Vitamin D3, Placebo
- Keywords
- severe asthma, vitamin D, treatment
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin D3Drug
Also called Cholecalciferol
Initial single dose 100000 IU, beginning from the second day 4000 IU/day for 24 weeks.
PlaceboDrug
Filling material: lactose monohydrate, cellulose, magnesium stearate
| Study group | Role | What they receive |
|---|---|---|
| Vitamin D3 | Experimental | Initial single dose 100000 IU, beginning from the second day 4000 IU/day for 24 weeks Receives: Drug: Vitamin D3 |
| Placebo | Placebo comparator | Amount of Placebo capsules corresponding to initial single dose of Vitamin D3, beginning from the second day amount of capsules corresponding to daily dose of Vitamin D for 24 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
relative dose reduction of ICS or OCS at week 24 as assessed by total ICS or OCS dose
Measured: 24 weeks
Secondary outcomes (8)
Exacerbations (rate of and time to first and subsequent exacerbations) as assessed by numbers of exacerbations
Measured: 24 weeks and 30 weeks
Asthma Control as assessed by ACQ score
Measured: at weeks 4, 8, 12, 14, 18, 20, 24, and 28
Asthma Quality of Life as assessed by the Mini-AQLQ score
Measured: at weeks 12, 18, 24 and 28
Pulmonary function test results as assessed by FEV1, FVC, IC, RV, TLC, and airway resistance
Measured: at weeks 4, 8, 12, 14, 18, 20, 24, and 28
Levels of vitamin D as assessed by serum concentrations
Measured: at weeks 12, 18, 24 and 28
Proportion of patients that achieved vitamin D sufficiency
Measured: at week 24
Assessment of safety and tolerability as assessed by number of adverse events
Measured: up to 30 weeks
Dyspnea as assessed by Baseline and Transition Dyspnea Indexes
Measured: at weeks 12, 18, 24 and 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2015 (estimated)
- Study start26 Jun 2015
- Primary completion9 Feb 2017
- Study completion9 Mar 2017
Why it stopped: recruitment problems
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johannes Gutenberg University Mainz
- Sponsor type
- University, hospital or other
- Collaborators
- German Federal Ministry of Education and Research
- Responsible party
- Principal investigator, PD Dr. Stephanie Korn, Johannes Gutenberg University Mainz
- Investigators
- Stephanie Korn, MD, Principal investigator, Johannes Gutenberg University Mainz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02424552
- Sponsor's protocol ID
- 2014-003
- Other IDs
- 2014-002363-15, 2014
- Acronym
- EVITA
- Status last verified
- Apr 2017
- First submitted
- 14 Apr 2015
- Last updated
- 1 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Korn S, Hubner M, Jung M, Blettner M, Buhl R. Severe and uncontrolled adult asthma is associated with vitamin D insufficiency and deficiency. Respir Res. 2013 Feb 22;14(1):25. doi: 10.1186/1465-9921-14-25.
PubMed 23432854Martineau AR, MacLaughlin BD, Hooper RL, Barnes NC, Jolliffe DA, Greiller CL, Kilpin K, McLaughlin D, Fletcher G, Mein CA, Hoti M, Walton R, Grigg J, Timms PM, Rajakulasingam RK, Bhowmik A, Rowe M, Venton TR, Choudhury AB, Simcock DE, Sadique Z, Monteiro WR, Corrigan CJ, Hawrylowicz CM, Griffiths CJ. Double-blind randomised placebo-controlled trial of bolus-dose vitamin D3 supplementation in adults with asthma (ViDiAs). Thorax. 2015 May;70(5):451-7. doi: 10.1136/thoraxjnl-2014-206449. Epub 2015 Feb 27.
PubMed 25724847Castro M, King TS, Kunselman SJ, Cabana MD, Denlinger L, Holguin F, Kazani SD, Moore WC, Moy J, Sorkness CA, Avila P, Bacharier LB, Bleecker E, Boushey HA, Chmiel J, Fitzpatrick AM, Gentile D, Hundal M, Israel E, Kraft M, Krishnan JA, LaForce C, Lazarus SC, Lemanske R, Lugogo N, Martin RJ, Mauger DT, Naureckas E, Peters SP, Phipatanakul W, Que LG, Sheshadri A, Smith L, Solway J, Sullivan-Vedder L, Sumino K, Wechsler ME, Wenzel S, White SR, Sutherland ER; National Heart, Lung, and Blood Institute's AsthmaNet. Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial. JAMA. 2014 May;311(20):2083-91. doi: 10.1001/jama.2014.5052.
PubMed 24838406
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- EVITA Trial: Effect of VItamin D as add-on Therapy for Vitamin D Insufficient Patients With Severe Asthma: a Randomized, Double-blind, Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT02424552
- Acronym / sponsor ID
- EVITA / 2014-003
- Conditions
- Asthma
- Keywords
- severe asthma, vitamin D, treatment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: recruitment problems
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Johannes Gutenberg University MainzUniversity, hospital or other
- Collaborators
- German Federal Ministry of Education and Research
- Study start
- 26 Jun 2015 (actual)
- Primary completion
- 9 Feb 2017 (actual)
- Study completion
- 9 Mar 2017 (actual)
- First posted
- 23 Apr 2015 (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.
The purpose of the EVITA trial is to compare the effects of vitamin D therapy with placebo on reducing the dose of inhaled or oral corticosteroids in patients with severe asthma and vitamin D insufficiency.
Detailed description
Patients with severe asthma represent the greatest unmet medical need among the asthmatic population, in particular due to their high risk of severe exacerbations. A substantial proportion of these patients does not achieve asthma control despite even high-dose ICS and LABA treatment, necessitating add-on therapy. For these patients oral corticosteroids (OCS) are a preferred treatment modality, which will inevitably lead to severe side effects. A high Proportion of patients with severe Asthma are Vitamin D insufficient (< 30 ng/ml). It is therefore tempting to speculate that vitamin D substitution in vitamin D insufficient patients who continue to experience suboptimal asthma control on ICS and LABA or ICS/LABA plus OCS treatment may boost corticosteroid responsiveness, thereby potentially reducing corticosteroid dose requirements and improving key parameters of asthma control.
The present study is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of treatment with vitamin D at a dose of 4000 IU/day administered daily following a single loading dose of 100 000 IU upon study entry over a period of 24 weeks in patients with severe asthma and vitamin D insufficiency. During the study, all patients will remain on their existing maintenance asthma therapy throughout the study, in addition to the study treatment, while reducing inhaled or oral steroids according to study protocol. The study consists of a 2-week run-in period, a 24 week double-blind treatment period including a 12 week steroid stable phase and two steroid reduction phases, followed by a follow-up visit 4 weeks after last study medication intake. The active treatment arm in this study will be standard of care plus vitamin D (loading dose of 100 000 IU upon study entry, to be followed by 4000 IU/day for the rest of the study period) while the comparator arm will be standard of care plus placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vitamin D3 | Experimental | Drug: Vitamin D3Initial single dose 100000 IU, beginning from the second day 4000 IU/day for 24 weeks |
| Placebo | Placebo comparator | Drug: PlaceboAmount of Placebo capsules corresponding to initial single dose of Vitamin D3, beginning from the second day amount of capsules corresponding to daily dose of Vitamin D for 24 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female patients, age ≥ 18 years
- A pulmonary specialist documented diagnosis of severe asthma according to the Global Initiative for Asthma and the German Asthma Network (GAN, www.german-asthma-net.de)
- Treatment with long-acting β2-agonists (LABA) and inhaled corticosteroids (ICS) at a dose of at least 1000 µg beclomethasone (or equivalent) per day, - chronic oral corticosteroid (OCS) use is allowed Stable asthma medication for ≥1 month prior to screening (≥4 months for omalizumab)
- Asthma Control Questionnaire (ACQ-5) score ≥ 1.5
- Vitamin D insufficiency as defined by a serum vitamin D concentration of < 30 ng/ml but ≥ 10 ng/ml at screening
Key exclusion criteria (5 listed)
- Patients on vitamin D substitution
- Current smokers or ex-smokers with a smoking history of more than 10 pack-years
- Pregnant or nursing women or women who intend to become pregnant during the study
- Known impaired renal function (GFR < 30 ml/min) and history of physician-diagnosed nephrolithiasis
- Use of other investigational drugs during the study or within 30 days of screening
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 |
|---|---|---|
| Vitamin D3Also: CholecalciferolInitial single dose 100000 IU, beginning from the second day 4000 IU/day for 24 weeks. | Drug | Vitamin D3 |
| PlaceboFilling material: lactose monohydrate, cellulose, magnesium stearate | Drug | Placebo |
Primary outcome
relative dose reduction of ICS or OCS at week 24 as assessed by total ICS or OCS dose
Time frame: 24 weeks
8 secondary outcomes
Exacerbations (rate of and time to first and subsequent exacerbations) as assessed by numbers of exacerbations
Time frame: 24 weeks and 30 weeks
Asthma Control as assessed by ACQ score
Time frame: at weeks 4, 8, 12, 14, 18, 20, 24, and 28
Asthma Quality of Life as assessed by the Mini-AQLQ score
Time frame: at weeks 12, 18, 24 and 28
Pulmonary function test results as assessed by FEV1, FVC, IC, RV, TLC, and airway resistance
Time frame: at weeks 4, 8, 12, 14, 18, 20, 24, and 28
Levels of vitamin D as assessed by serum concentrations
Time frame: at weeks 12, 18, 24 and 28
Proportion of patients that achieved vitamin D sufficiency
Time frame: at week 24
Assessment of safety and tolerability as assessed by number of adverse events
Time frame: up to 30 weeks
Dyspnea as assessed by Baseline and Transition Dyspnea Indexes
Time frame: at weeks 12, 18, 24 and 28
Results and safety
The study was stopped early (reason given: recruitment problems). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2017.
- Background: PubMed 23432854Korn S, Hubner M, Jung M, Blettner M, Buhl R. Severe and uncontrolled adult asthma is associated with vitamin D insufficiency and deficiency. Respir Res. 2013 Feb 22;14(1):25. doi: 10.1186/1465-9921-14-25.
- Background: PubMed 25724847Martineau AR, MacLaughlin BD, Hooper RL, Barnes NC, Jolliffe DA, Greiller CL, Kilpin K, McLaughlin D, Fletcher G, Mein CA, Hoti M, Walton R, Grigg J, Timms PM, Rajakulasingam RK, Bhowmik A, Rowe M, Venton TR, Choudhury AB, Simcock DE, Sadique Z, Monteiro WR, Corrigan CJ, Hawrylowicz CM, Griffiths CJ. Double-blind randomised placebo-controlled trial of bolus-dose vitamin D3 supplementation in adults with asthma (ViDiAs). Thorax. 2015 May;70(5):451-7. doi: 10.1136/thoraxjnl-2014-206449. Epub 2015 Feb 27.
- Background: PubMed 24838406Castro M, King TS, Kunselman SJ, Cabana MD, Denlinger L, Holguin F, Kazani SD, Moore WC, Moy J, Sorkness CA, Avila P, Bacharier LB, Bleecker E, Boushey HA, Chmiel J, Fitzpatrick AM, Gentile D, Hundal M, Israel E, Kraft M, Krishnan JA, LaForce C, Lazarus SC, Lemanske R, Lugogo N, Martin RJ, Mauger DT, Naureckas E, Peters SP, Phipatanakul W, Que LG, Sheshadri A, Smith L, Solway J, Sullivan-Vedder L, Sumino K, Wechsler ME, Wenzel S, White SR, Sutherland ER; National Heart, Lung, and Blood Institute's AsthmaNet. Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial. JAMA. 2014 May;311(20):2083-91. doi: 10.1001/jama.2014.5052.
- Individual participant dataSharing planned: Undecided
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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.
Stephanie Korn, MD principal investigator
Johannes Gutenberg University Mainz
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Vitamin D3 in people with Asthma, run by Johannes Gutenberg University Mainz at 9 sites in Germany.
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 5 inclusion and 5 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: stopped early, as of the sponsor's last update on 1 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Germany. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: recruitment problems). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
relative dose reduction of ICS or OCS at week 24 as assessed by total ICS or OCS dose (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02424552, which also lists 3 linked publications.
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 1 May 2017.