Chronic Obstructive Pulmonary DiseasePhase 2DISARMNCT02833480
A Study to Investigate the Differential Effects of Inhaled Symbicort and Advair on Lung Microbiota
A Phase 2 study testing Fluticasone group, Budesonide group and Formoterol group in people with Chronic Obstructive Pulmonary Disease, run by University of British Columbia at 2 sites in Canada.
Trial summary
This study will evaluate the effects of budesonide (using Symbicort which is budesonide and formoterol) and fluticasone (using Advair which is fluticasone and salmeterol) on the airway microorganisms of patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- Fluticasone group, Budesonide group and Formoterol group
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 2 sitesCanada
- Study dates
- Feb 2015to Jun 2021
- Phase
- Phase 2
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of informed consent prior to any study specific procedures.
- History of moderate to very severe COPD with a post-bronchodilator forced expiratory volume/forced vital capacity (FEV1/FVC) <0.70 and a post-bronchodilator FEV1>20% and ≤80% of predicted normal value at screening.
- Current smoker or ex-smoker with a tobacco history of ≥10 pack-years (1 pack year= 20 cigarettes smoked per day for 1 year).
Who cannot join
- Clinically important pulmonary disease other than COPD (e.g. active lung infection, clinically significant bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, and primary ciliary dyskinesia) and/ or radiological findings suggestive of a respiratory disease other than COPD that is contributing to the subject's respiratory symptoms.
- Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could:
- Affect the safety of the subject throughout the study
- Influence the findings of the study or their interpretation
- Impede the subject's ability to complete the entire duration of study Subjects who have epilepsy must be on a stable dose of medication for 30 days prior to Visit 4.
- Unstable ischemic heart disease, or uncontrolled arrhythmia, cardiomyopathy, heart failure, and renal failure, or uncontrolled hypertension as defined by the Investigator, or any other relevant cardiovascular disorder as judged by the Investigator
Show all 19Show fewer
- Treatment with systemic corticosteroids and/or antibiotics, and/or hospitalization for a COPD exacerbation within 8 weeks prior to enrolment (Visit 1), based on last dose of steroids or last date of hospitalization whatever occurred later.
- Acute upper or lower respiratory infection requiring antibiotics or antiviral medication within 2 weeks prior to enrolment (Visit 1).
- Pneumonia within 8 weeks prior to enrolment (Visit 1), based on the last day of antibiotic treatment or hospitalization date, whatever occurred later.
- Pregnant, breastfeeding, or lactating women.
- Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening/run-in period, which, in the opinion of the Investigator, may put the subject at risk because of his/her participation in the study, or may influence the results of the study, or the subject's ability to complete entire duration of the study.
- Use of immunosuppressive medication, including rectal corticosteroids, high potency topical corticosteroids and systemic steroids within 28 days prior to randomization.
- Receipt of blood products within 30 days prior to enrollment (Visit 1).
- Receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to Visit 1.
- History of alcohol or drug abuse within the past year, which may compromise the study data interpretation as judged by Investigator or Study Physician.
- Subjects who in the opinion of the investigator or qualified designee have evidence of active tuberculosis (TB), either treated or untreated.
- Scheduled in-patient hospitalization or surgical procedure during the course of the study.
- Asthma as a primary or main diagnosis according to the Global Initiative for Asthma (GINA, http://www.ginasthma.org/) guidelines or other accepted guidelines. Subjects with a past medical history of asthma (e.g. childhood or adolescence) may be included.
- The male partner of someone who may become pregnant during the course of the study
Trial locations and contacts
2 sites in 1 country.
Canada2 sites, 2 recruiting
- Recruiting
St. Paul's Hospital
Vancouver, British Columbia, V6Z1Y6
Lynda Lazosky, 604-682-2344 ext. 64884, llazosky@providencehealth.bc.ca
Don Sin, MD
- Recruiting
BC Cancer Agency
Vancouver, British Columbia
Amy English, aenglish@bccrc.ca
Stephen Lam, MD
About this study
This study will evaluate the effects of budesonide (using Symbicort which is budesonide and formoterol) and fluticasone (using Advair which is fluticasone and salmeterol) on the airway microorganisms of patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). This is a randomized, parallel group, two-centered clinical trial study to evaluate the effects of a 12 week treatment with Symbicort 400 mcg BID and Advair 250 mcg BID (via Diskus) on airway microbiota in patients with moderate-to-severe COPD. The control arm of this study will be Oxeze 12 ug BID.
Read the detailed description
This is a randomized, non-placebo controlled study to evaluate the effects of Symbicort 400 mcg twice daily (BID) and Advair 250 mcg BID over 12 weeks. As the standard of therapy for COPD is a long-acting muscarinic antagonist (LAMA) treatment, a placebo only group cannot be ethically justified. The control arm of this study will thus be Oxeze 12 ug BID. The study will recruit approximately 69 subjects, from St. Paul's Hospital and British Columbia Cancer Agency, randomized 1:1:1 to the 3 arms in blocks. We anticipate 10 to 15% drop out rate, which will enable approximately 60 subjects for full analysis.
After the initial enrolment and confirmation of the entry criteria, subjects will perform spirometry before and following bronchodilation with salbutamol (up to 400 ug). They will then enter a 4-week run-in period during which all subjects will be withdrawn from inhaled corticosteroid containing products. They will then be treated with formoterol via Turbuhaler 12 ug BID and short-acting beta-2 agonists as needed (PRN). Subjects may also have LAMA (either tiotropium 18 ug once daily or glycopyrronium 50 ug once daily) at the discretion of the attending physician. At the end of the run-in phase, eligibility will be confirmed and then subjects will undergo pre and post-spirometry, low-dose thoracic computed tomography (CT) and bronchoscopy. One week post-bronchoscopy, the subjects will be randomized to a 12-week treatment period. Subjects may also have LAMA at the discretion of the attending physician. At the end of the 12 week treatment period, the subjects will undergo pre- and post-spirometry and 2nd bronchoscopy. The subjects will be re-evaluated one week following bronchoscopy and then discharged from the study. All subjects with pulmonary nodule requiring follow-up will be evaluated by the attending physician and the pulmonary nodule will be investigated as per guidelines of the Fleischner Society.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- Fluticasone group, Budesonide group, Formoterol group
- 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.
Fluticasone groupDrug
Also called Advair
Budesonide groupDrug
Also called Symbicort
Formoterol groupDrug
Also called Oxeze
| Study group | Role | What they receive |
|---|---|---|
| Fluticasone group | Experimental | Advair (fluticasone) 250 mcg to be administered twice daily via Diskus for 12 weeks Receives: Drug: Fluticasone group |
| Budesonide group | Experimental | Symbicort (budesonide) 400 mcg to be administered twice daily via Turbuhaler for 12 weeks Receives: Drug: Budesonide group |
| Formoterol group | Active comparator | Oxeze (formoterol) 12 microg to be administered twice daily via Turbuhaler for 12 weeks Receives: Drug: Formoterol group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in total bacterial population in the bronchoalveolar lavage fluid
Measured: 12 weeks
Change in bacterial diversity using Shannon Index based on 16S sequencing.
Measured: 12 weeks
Secondary outcomes (9)
Change in bacterial membership using Beta-diversity
Measured: 12 weeks
Characterization of bacteria Operational Taxonomic Unit
Measured: 12 weeks
Change in total cell count in bronchoalveolar lavage fluid
Measured: 12 weeks
Change in total neutrophil count in bronchoalveolar lavage fluid
Measured: 12 weeks
Change in total lymphocyte count in bronchoalveolar lavage fluid
Measured: 12 weeks
Change in total mono-macrophage count in bronchoalveolar lavage fluid
Measured: 12 weeks
Change in St. George's Respiratory Questionnaire
Measured: 12 weeks
Change in forced expiratory volume in 1 second
Measured: 12 weeks
Change in forced vital capacity
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2016 (estimated)
- Study startFeb 2015
- Primary completionJan 2021 (estimated)
- Study completionJun 2021 (estimated)
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 Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 69 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Principal investigator, Don Sin, University of British Columbia
- Investigators
- Don Sin, MD, Principal investigator, St. Paul's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02833480
- Sponsor's protocol ID
- H14-02277
- Acronym
- DISARM
- Status last verified
- Mar 2020
- First submitted
- 26 May 2016
- Last updated
- 30 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Ho CG, Milne S, Li X, Yang CX, Leitao Filho FS, Cheung CY, Yang JSW, Hernandez Cordero AI, Yang CWT, Shaipanich T, van Eeden SF, Leung JM, Lam S, Sin DD. Airway Eosinophilia on Bronchoalveolar Lavage and the Risk of Exacerbations in COPD. Biomedicines. 2022 Jun 15;10(6):1412. doi: 10.3390/biomedicines10061412.
PubMed 35740433Akata K, Leung JM, Yamasaki K, Leitao Filho FS, Yang J, Xi Yang C, Takiguchi H, Shaipanich T, Sahin B, Whalen BA, Yang CWT, Sin DD, van Eeden SF. Altered Polarization and Impaired Phagocytic Activity of Lung Macrophages in People With Human Immunodeficiency Virus and Chronic Obstructive Pulmonary Disease. J Infect Dis. 2022 Mar 2;225(5):862-867. doi: 10.1093/infdis/jiab506.
PubMed 34610114Leitao Filho FS, Takiguchi H, Akata K, Ra SW, Moon JY, Kim HK, Cho Y, Yamasaki K, Milne S, Yang J, Yang CWT, Li X, Nislow C, van Eeden SF, Shaipanich T, Lam S, Leung JM, Sin DD. Effects of Inhaled Corticosteroid/Long-Acting beta2-Agonist Combination on the Airway Microbiome of Patients with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Clinical Trial (DISARM). Am J Respir Crit Care Med. 2021 Nov 15;204(10):1143-1152. doi: 10.1164/rccm.202102-0289OC.
PubMed 34464242
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Investigate the Differential Effects of Inhaled Symbicort and Advair on Lung Microbiota
- ClinicalTrials.gov ID
- NCT02833480
- Acronym / sponsor ID
- DISARM / H14-02277
- Conditions
- Chronic Obstructive Pulmonary Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 69 participants (estimated)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Feb 2015
- Primary completion
- Jan 2021 (estimated)
- Study completion
- Jun 2021 (estimated)
- First posted
- 14 Jul 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.
This study will evaluate the effects of budesonide (using Symbicort which is budesonide and formoterol) and fluticasone (using Advair which is fluticasone and salmeterol) on the airway microorganisms of patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). This is a randomized, parallel group, two-centered clinical trial study to evaluate the effects of a 12 week treatment with Symbicort 400 mcg BID and Advair 250 mcg BID (via Diskus) on airway microbiota in patients with moderate-to-severe COPD. The control arm of this study will be Oxeze 12 ug BID.
Detailed description
This is a randomized, non-placebo controlled study to evaluate the effects of Symbicort 400 mcg twice daily (BID) and Advair 250 mcg BID over 12 weeks. As the standard of therapy for COPD is a long-acting muscarinic antagonist (LAMA) treatment, a placebo only group cannot be ethically justified. The control arm of this study will thus be Oxeze 12 ug BID. The study will recruit approximately 69 subjects, from St. Paul's Hospital and British Columbia Cancer Agency, randomized 1:1:1 to the 3 arms in blocks. We anticipate 10 to 15% drop out rate, which will enable approximately 60 subjects for full analysis.
After the initial enrolment and confirmation of the entry criteria, subjects will perform spirometry before and following bronchodilation with salbutamol (up to 400 ug). They will then enter a 4-week run-in period during which all subjects will be withdrawn from inhaled corticosteroid containing products. They will then be treated with formoterol via Turbuhaler 12 ug BID and short-acting beta-2 agonists as needed (PRN). Subjects may also have LAMA (either tiotropium 18 ug once daily or glycopyrronium 50 ug once daily) at the discretion of the attending physician. At the end of the run-in phase, eligibility will be confirmed and then subjects will undergo pre and post-spirometry, low-dose thoracic computed tomography (CT) and bronchoscopy. One week post-bronchoscopy, the subjects will be randomized to a 12-week treatment period. Subjects may also have LAMA at the discretion of the attending physician. At the end of the 12 week treatment period, the subjects will undergo pre- and post-spirometry and 2nd bronchoscopy. The subjects will be re-evaluated one week following bronchoscopy and then discharged from the study. All subjects with pulmonary nodule requiring follow-up will be evaluated by the attending physician and the pulmonary nodule will be investigated as per guidelines of the Fleischner Society.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Fluticasone group | Experimental | Drug: Fluticasone groupAdvair (fluticasone) 250 mcg to be administered twice daily via Diskus for 12 weeks |
| Budesonide group | Experimental | Drug: Budesonide groupSymbicort (budesonide) 400 mcg to be administered twice daily via Turbuhaler for 12 weeks |
| Formoterol group | Active comparator | Drug: Formoterol groupOxeze (formoterol) 12 microg to be administered twice daily via Turbuhaler for 12 weeks |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Provision of informed consent prior to any study specific procedures.
- History of moderate to very severe COPD with a post-bronchodilator forced expiratory volume/forced vital capacity (FEV1/FVC) <0.70 and a post-bronchodilator FEV1>20% and ≤80% of predicted normal value at screening.
- Current smoker or ex-smoker with a tobacco history of ≥10 pack-years (1 pack year= 20 cigarettes smoked per day for 1 year).
Key exclusion criteria (19 listed)
- Clinically important pulmonary disease other than COPD (e.g. active lung infection, clinically significant bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, and primary ciliary dyskinesia) and/ or radiological findings suggestive of a respiratory disease other than COPD that is contributing to the subject's respiratory symptoms.
- Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could:
- Unstable ischemic heart disease, or uncontrolled arrhythmia, cardiomyopathy, heart failure, and renal failure, or uncontrolled hypertension as defined by the Investigator, or any other relevant cardiovascular disorder as judged by the Investigator
- Treatment with systemic corticosteroids and/or antibiotics, and/or hospitalization for a COPD exacerbation within 8 weeks prior to enrolment (Visit 1), based on last dose of steroids or last date of hospitalization whatever occurred later.
- Acute upper or lower respiratory infection requiring antibiotics or antiviral medication within 2 weeks prior to enrolment (Visit 1).
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 |
|---|---|---|
| Fluticasone groupAlso: Advair | Drug | Fluticasone group |
| Budesonide groupAlso: Symbicort | Drug | Budesonide group |
| Formoterol groupAlso: Oxeze | Drug | Formoterol group |
Primary outcome
Change in total bacterial population in the bronchoalveolar lavage fluid
Time frame: 12 weeks
Change in bacterial diversity using Shannon Index based on 16S sequencing.
Time frame: 12 weeks
9 secondary outcomes
Change in bacterial membership using Beta-diversity
Time frame: 12 weeks
Characterization of bacteria Operational Taxonomic Unit
Time frame: 12 weeks
Change in total cell count in bronchoalveolar lavage fluid
Time frame: 12 weeks
Change in total neutrophil count in bronchoalveolar lavage fluid
Time frame: 12 weeks
Change in total lymphocyte count in bronchoalveolar lavage fluid
Time frame: 12 weeks
Change in total mono-macrophage count in bronchoalveolar lavage fluid
Time frame: 12 weeks
Change in St. George's Respiratory Questionnaire
Time frame: 12 weeks
Change in forced expiratory volume in 1 second
Time frame: 12 weeks
Change in forced vital capacity
Time frame: 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2020.
- Derived from this study: PubMed 35740433Ho CG, Milne S, Li X, Yang CX, Leitao Filho FS, Cheung CY, Yang JSW, Hernandez Cordero AI, Yang CWT, Shaipanich T, van Eeden SF, Leung JM, Lam S, Sin DD. Airway Eosinophilia on Bronchoalveolar Lavage and the Risk of Exacerbations in COPD. Biomedicines. 2022 Jun 15;10(6):1412. doi: 10.3390/biomedicines10061412.
- Derived from this study: PubMed 34610114Akata K, Leung JM, Yamasaki K, Leitao Filho FS, Yang J, Xi Yang C, Takiguchi H, Shaipanich T, Sahin B, Whalen BA, Yang CWT, Sin DD, van Eeden SF. Altered Polarization and Impaired Phagocytic Activity of Lung Macrophages in People With Human Immunodeficiency Virus and Chronic Obstructive Pulmonary Disease. J Infect Dis. 2022 Mar 2;225(5):862-867. doi: 10.1093/infdis/jiab506.
- Derived from this study: PubMed 34464242Leitao Filho FS, Takiguchi H, Akata K, Ra SW, Moon JY, Kim HK, Cho Y, Yamasaki K, Milne S, Yang J, Yang CWT, Li X, Nislow C, van Eeden SF, Shaipanich T, Lam S, Leung JM, Sin DD. Effects of Inhaled Corticosteroid/Long-Acting beta2-Agonist Combination on the Airway Microbiome of Patients with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Clinical Trial (DISARM). Am J Respir Crit Care Med. 2021 Nov 15;204(10):1143-1152. doi: 10.1164/rccm.202102-0289OC.
- Individual participant dataSharing planned: No
Related trials for Chronic Obstructive Pulmonary Disease
Active, not recruiting
Symptoms and Functions in Patients With COPD and Chronic Bronchitis Switching From CIG to THS
COPD, Smoking
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruiting
The Aim of the Study is to Decipher the Alterations in Signalling Pathways of Skeletal Muscle Stem Cells (Satellite Cells (SCs)) in Individuals With COPD, as Well as to Examine the Effect of Exercise Training on SCs.
COPD (Chronic Obstructive Pulmonary Disease), Sarcopenia in Elderly
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of Belumosudil Compared With Best Available Therapy in Participants Aged 12 Years or Older With Chronic Graft-versus-host Disease
Chronic Graft Versus Host Disease
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.
Don Sin, MD principal investigator
St. Paul's Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fluticasone group, Budesonide group and Formoterol group in people with Chronic Obstructive Pulmonary Disease, run by University of British Columbia at 2 sites in Canada.
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 3 inclusion and 19 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 30 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Lynda Lazosky (604-682-2344 ext. 64884, llazosky@providencehealth.bc.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in total bacterial population in the bronchoalveolar lavage fluid (time frame: 12 weeks). The study lists 2 primary outcomes in all. 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 NCT02833480, 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 30 Mar 2020.