Sarcoidosis; Antimycobacterial TherapyPhase 2NCT02024555
Phase II Investigation of Antimycobacterial Therapy on Progressive, Pulmonary Sarcoidosis
A Phase 2 study testing Levofloxacin, Ethambutol and Azithromycin in people with Sarcoidosis; Antimycobacterial Therapy, run by Vanderbilt University at 6 sites in United States.
Trial summary
The primary purpose of this study is to investigate the efficacy and safety of oral antimycobacterial therapy in patients with confirmed progressive pulmonary sarcoidosis. We suspect that the CLEAR regimen will improve the absolute FVC percent predicted in chronic pulmonary sarcoidosis participants. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sarcoidosis; Antimycobacterial Therapy
- What is being tested?
- Levofloxacin, Ethambutol and Azithromycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 97 participants
- Where
- 6 sitesUnited States
- Study dates
- Mar 2014to 1 Apr 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients with sarcoidosis as defined by the ATS/ERS/WASOG statement on sarcoidosis as defined by the clinical presentation consistent with sarcoidosis, as well as biopsy demonstrating granulomas, and no alternative for the cause of the granulomas, such as tuberculosis for at least one year prior to randomization.
- Evidence of disease progression as defined by at least one of the following three criteria:
- Decline of absolute percent predicted of FVC (FVC ≥45% or higher of predicted value) or DLCO of at least 5% on serial measurements (DLCO range >35%, if measured); Radiographic progression in chest imaging on side by side comparison; Change in dyspnea score, as measured by Transition Dyspnea Index (TDI); Positive peripheral immune responses to ESAT-6 as a biomarker of response to CLEAR regimen.
- Possess evidence of parenchymal or nodal disease on chest radiograph.
Who cannot join
- Inability to obtain consent
- Age less than 18 years
- Female participants of childbearing potential not willing to use one of the following methods of birth control for the duration of the study and 90 days after study completion: condoms, sponge, foams, jellies, diaphragm, non-hormonal intrauterine device, a vasectomized sole partner or abstinence. Note: Oral contraceptive pills are not effective birth control when taking rifamycin. A negative urine pregnancy test at screening visit if female of childbearing potential
- FVC predicted value is < 45%.
- End-stage fibrotic pulmonary disease.
- Significant underlying liver disease.
Show all 24Show fewer
- Allergy or intolerance to any of the antibiotics within the CLEAR regimen.
- Allergy or intolerance to albuterol
- Poor venous access for obtaining blood samples
- History of active tuberculosis, close contact with a person with active tuberculosis within the 6 months prior to the screening visit or has a positive PPD.
- Significant disorder, other than sarcoidosis, that would complicate the treatment evaluation, (such as respiratory, cardiac, neurologic, musculoskeletal or seizure disorders)
- Use of an investigational drug within 30 days prior to screening or within 5 half-lives of the agent, whichever is longer.
- Currently receiving >40mg prednisone.
- ALT or AST >5 times upper limit of normal (ULN)
- Leukopenia, as defined by WBC <3.0 cells/mm3 or absolute neutrophil count <1000
- Breast feeding.
- Color perception impairment as defined by the inability to differentiate colors per personal history or history of optic neuritis from any cause, including from sarcoidosis.
- If patient is on immunomodulators, they must be on regimen for ≥ 3-month period and on a stable dose for > 4 weeks.
- Family or personal history of long QT interval
- Most recent nuclear medicine scan or echocardiogram (if done), demonstrating cardiac ejection fraction <35%
- Participant has persistent or active infection(s) requiring hospitalization or treatment with antibiotics, antiretrovirals, or antifungals within 30 days prior to baseline. Minocycline and doxycycline are not considered antibiotics when used to treat sarcoidosis.
- Any significant finding in the patient's medical history or physical or psychiatric exam prior to or after randomization that, in the opinion of the investigator, would affect patient safety or compliance or ability to deliver the study drug according to protocol.
- On medications that interact with the antibiotics of the CLEAR regimen
- History of or receiving treatment for pulmonary hypertension. Receiving biologic medication within the 6 months prior to screening visit
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Albany Medical Center
Albany, New York, 12208
Medical University of South Carolina
Charleston, South Carolina, 29425
University of Cincinnati
Cincinnati, Ohio, 45267
Cleveland Clinic
Cleveland, Ohio, 44195
Ohio State University
Columbus, Ohio, 43221
Vanderbilt University School of Medicine
Nashville, Tennessee, 37232
About this study
Official title: Investigation of the Efficacy of Antimycobacterial Therapy on Pulmonary Sarcoidosis Phase II Randomized, Double-blind, Placebo-controlled Trial
The primary purpose of this study is to investigate the efficacy and safety of oral antimycobacterial therapy in patients with confirmed progressive pulmonary sarcoidosis. We suspect that the CLEAR regimen will improve the absolute FVC percent predicted in chronic pulmonary sarcoidosis participants.
Read the detailed description
Primary Objective: To assess the efficacy and safety of oral CLEAR therapy in patients with confirmed progressive pulmonary sarcoidosis.
Hypothesis: The CLEAR regimen will improve the absolute FVC percent predicted in chronic pulmonary sarcoidosis participants by augmenting T cell responses through the normalization of p56Lck expression and IL-2 production.
- Conditions
- Sarcoidosis; Antimycobacterial Therapy
- Being tested
- Levofloxacin, Ethambutol, Azithromycin, Rifampin, Placebo
- Medical subject headings
- Sarcoidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevofloxacinDrug
Also called Levaquin
EthambutolDrug
AzithromycinDrug
Also called Z-pack
RifampinDrug
Also called Rifadin, Rimactane
PlaceboDrug
This will serve as a placebo to the antibiotics used in antimycobacterial therapy.
| Study group | Role | What they receive |
|---|---|---|
| Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin | Active comparator | Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Receives: Drug: Levofloxacin; Drug: Ethambutol; Drug: Azithromycin; Drug: Rifampin |
| Placebo | Placebo comparator | Riboflavin will be used for rifampin; encapsulated microcrystalline cellulose will be used to replace the levofloxacin, ethambutol and azithromycin.
The pill count will be the same as the comparator regimen. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Percent Predicted Absolute Forced Vital Capacity (FVC) in Participants With Pulmonary Sarcoidosis, Comparing Baseline With Performance After Completion of 16 Weeks of Therapy.
Change in percent predicted absolute forced vital capacity (FVC) in participants with pulmonary sarcoidosis, comparing baseline with performance after completion of 16 weeks of therapy. This will involve comparing sarcoidosis and placebo after 16 weeks of therapy.
Measured: Baseline to 16 weeks
Secondary outcomes (11)
Radiographic Improvement in Sarcoidosis Lung Disease by Frontal Chest X-ray .
Radiographic improvement in sarcoidosis lung disease by frontal chest x-ray . Local investigators will score chest x-rays.
Measured: Baseline and 16 weeks
Six Minute Walk, Distance in Meters
The 6-min walk test (6 MWT) is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes.
Measured: Baseline, 4, 8, and 16 and 24 weeks
Change in Oxygen Saturation
measured using pulse oximetry
Measured: Baseline, 4, 8, and 16 and 24 weeks
Change in Level of Dyspnea
Outcome measure if a composite
Measured: Baseline, 4, 8 and 16 weeks
Change in the Saint George's Respiratory Questionnaire (SGRQ)
The SGRQ is a 50-item questionnaire developed to measure health status (quality of life) in patients with diseases of airways obstruction.
Scores range from 0 to 100, with higher scores indicating more limitations.
A minimum change in score of 4 units was established as clinically relevant after patient and clinician testing.
Measured: Baseline and 16 weeks
Fatigue Assessment Scale (FAS).
The FAS is a 10-item general fatigue questionnaire to assess fatigue. Total scores can range from 10, indicating the lowest level of fatigue, to 50, denoting the highest.
Measured: Baseline, 4, 8, 16 and 24 weeks
Change in the King's Sarcoidosis Questionnaire (KSQ) for the Assessment of Health Status;
The KSQ is a free, online questionnaire to be filled out by sarcoidosis patients. The questionnaire takes around 10 minutes and is split into 5 sections; general health status, lungs, medication, skin and eyes. There are 29 questions in total, however some questions may not be answered (depending on the type of sarcoidosis affected). Each question asks patients to rate how they feel about many different aspects of their life, for instance how much pain they are in or how difficult they find everyday tasks. Information provided is confidential. Results are given as a number between 1-100 with higher numbers indicating better health.
Measured: Baseline and 16 weeks
Adverse Events
Safety profile of regimen as evidenced by the number of adverse events
Measured: 24 weeks
FEV1%
FEV1% was measure pre and post 6 minute walk test
Measured: Baseline, 4, 8, and 16 and 24 weeks
Failure of Standard Therapy
We will assess how many subjects in either arm need escalation of their standard regimen (ie increase in prednisone) during the 16 weeks.
Measured: Baseline to 16 weeks
Abnormal Lab Values
Safety profile of regimen as evidenced by the number of abnormal lab values classified as Adverse Events
Measured: baseline to 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2013 (estimated)
- Study startMar 2014
- Primary completion1 Apr 2019
- Study completion1 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Sarcoidosis; Antimycobacterial TherapyStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 97 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Wonder Drake, Vanderbilt University
- Investigators
- Wonder Drake, MD, Principal investigator, Vanderbilt University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02024555
- Sponsor's protocol ID
- R01HL117074
- Other IDs
- R01HL117074-01
- Status last verified
- Jun 2020
- First submitted
- 26 Dec 2013
- Last updated
- 9 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of the Efficacy of Antimycobacterial Therapy on Pulmonary Sarcoidosis Phase II Randomized, Double-blind, Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT02024555
- Acronym / sponsor ID
- R01HL117074
- Conditions
- Sarcoidosis; Antimycobacterial Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 97 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Mar 2014
- Primary completion
- 1 Apr 2019 (actual)
- Study completion
- 1 Apr 2019 (actual)
- First posted
- 31 Dec 2013 (estimated)
- Results
- Posted 9 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to investigate the efficacy and safety of oral antimycobacterial therapy in patients with confirmed progressive pulmonary sarcoidosis. We suspect that the CLEAR regimen will improve the absolute FVC percent predicted in chronic pulmonary sarcoidosis participants.
Detailed description
Primary Objective: To assess the efficacy and safety of oral CLEAR therapy in patients with confirmed progressive pulmonary sarcoidosis.
Hypothesis: The CLEAR regimen will improve the absolute FVC percent predicted in chronic pulmonary sarcoidosis participants by augmenting T cell responses through the normalization of p56Lck expression and IL-2 production.
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 |
|---|---|---|
| Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin | Active comparator | Drug: Levofloxacin, Drug: Ethambutol, Drug: Azithromycin, Drug: RifampinLevofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD |
| Placebo | Placebo comparator | Drug: PlaceboRiboflavin will be used for rifampin; encapsulated microcrystalline cellulose will be used to replace the levofloxacin, ethambutol and azithromycin. The pill count will be the same as the comparator regimen. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients with sarcoidosis as defined by the ATS/ERS/WASOG statement on sarcoidosis as defined by the clinical presentation consistent with sarcoidosis, as well as biopsy demonstrating granulomas, and no alternative for the cause of the granulomas, such as tuberculosis for at least one year prior to randomization.
- Evidence of disease progression as defined by at least one of the following three criteria:
- Decline of absolute percent predicted of FVC (FVC ≥45% or higher of predicted value) or DLCO of at least 5% on serial measurements (DLCO range >35%, if measured); Radiographic progression in chest imaging on side by side comparison; Change in dyspnea score, as measured by Transition Dyspnea Index (TDI); Positive peripheral immune responses to ESAT-6 as a biomarker of response to CLEAR regimen.
- Possess evidence of parenchymal or nodal disease on chest radiograph.
Key exclusion criteria (24 listed)
- Inability to obtain consent
- Age less than 18 years
- Female participants of childbearing potential not willing to use one of the following methods of birth control for the duration of the study and 90 days after study completion: condoms, sponge, foams, jellies, diaphragm, non-hormonal intrauterine device, a vasectomized sole partner or abstinence. Note: Oral contraceptive pills are not effective birth control when taking rifamycin. A negative urine pregnancy test at screening visit if female of childbearing potential
- FVC predicted value is < 45%.
- End-stage fibrotic pulmonary disease.
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 |
|---|---|---|
| LevofloxacinAlso: Levaquin | Drug | Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin |
| Ethambutol | Drug | Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin |
| AzithromycinAlso: Z-pack | Drug | Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin |
| RifampinAlso: Rifadin, Rimactane | Drug | Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin |
| PlaceboThis will serve as a placebo to the antibiotics used in antimycobacterial therapy. | Drug | Placebo |
Primary outcome
Change in Percent Predicted Absolute Forced Vital Capacity (FVC) in Participants With Pulmonary Sarcoidosis, Comparing Baseline With Performance After Completion of 16 Weeks of Therapy.
Time frame: Baseline to 16 weeks
Change in percent predicted absolute forced vital capacity (FVC) in participants with pulmonary sarcoidosis, comparing baseline with performance after completion of 16 weeks of therapy. This will involve comparing sarcoidosis and placebo after 16 weeks of therapy.
11 secondary outcomes
Radiographic Improvement in Sarcoidosis Lung Disease by Frontal Chest X-ray .
Time frame: Baseline and 16 weeks
Six Minute Walk, Distance in Meters
Time frame: Baseline, 4, 8, and 16 and 24 weeks
Change in Oxygen Saturation
Time frame: Baseline, 4, 8, and 16 and 24 weeks
Change in Level of Dyspnea
Time frame: Baseline, 4, 8 and 16 weeks
Change in the Saint George's Respiratory Questionnaire (SGRQ)
Time frame: Baseline and 16 weeks
Fatigue Assessment Scale (FAS).
Time frame: Baseline, 4, 8, 16 and 24 weeks
Change in the King's Sarcoidosis Questionnaire (KSQ) for the Assessment of Health Status;
Time frame: Baseline and 16 weeks
Adverse Events
Time frame: 24 weeks
FEV1%
Time frame: Baseline, 4, 8, and 16 and 24 weeks
Failure of Standard Therapy
Time frame: Baseline to 16 weeks
Abnormal Lab Values
Time frame: baseline to 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Sarcoidosis; Antimycobacterial Therapy
Active, not recruiting
the PHENOSAR Trial: Use of Antibiotics in Treatment of Sarcoidosis
Sarcoidosis, Pulmonary, Sarcoidosis Skin
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.
Wonder Drake, MD principal investigator
Vanderbilt University School of Medicine
6 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 Levofloxacin, Ethambutol and Azithromycin in people with Sarcoidosis; Antimycobacterial Therapy, run by Vanderbilt University at 6 sites in United States.
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 4 inclusion and 24 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: finished, as of the sponsor's last update on 9 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. 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 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?
Yes. Results are posted in the registry (first posted 9 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Percent Predicted Absolute Forced Vital Capacity (FVC) in Participants With Pulmonary Sarcoidosis, Comparing Baseline With Performance After Completion of 16 Weeks of Therapy. (time frame: Baseline to 16 weeks). 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 9 Jul 2020.