EmphysemaPhase 4LEEPNCT02696564
Losartan Effects on Emphysema Progression
A Phase 4 study testing Losartan in people with Emphysema, run by JHSPH Center for Clinical Trials at 28 sites in United States.
Trial summary
A randomized, parallel, placebo controlled trial to evaluate the effect of 100mg/day losartan on the progression of emphysema as measured by quantitative HRCT compared to placebo . Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Emphysema
- What is being tested?
- Losartan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 220 participants
- Where
- 28 sitesUnited States
- Study dates
- 23 May 2017to 30 Jun 2021
- Phase
- Phase 4
- 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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Mild to severe COPD: Ratio of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) less than or equal to 0.70, FEV1 20-80% of predicted
- Current or former smoker
- HRCT scan with 5-35% of voxels with density less than -950 Hounsfield Units (HU)
- Ability to understand and willingness to sign consent documents
Who cannot join
- Current therapy with angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)
- Known intolerance to ACE inhibitor or ARB
- History of angioedema
- Conventional indication for ACE inhibitor or ARB (e.g., history of myocardial infarction, known cardiomyopathy)
- Renal insufficiency (GFR <30 mL/min by Cockcroft-Gault calculation)
- Current regular use of NSAIDs defined as daily use 5 or more days of the week for more than one month
Show all 22Show fewer
- Potassium supplementation or serum potassium level of 5.0 milliequivalents (mEq)/dL or higher at V1
- Current use of a potassium sparing diuretic
- COPD exacerbation requiring treatment within 6 weeks at V1
- Chronic systemic corticosteroid use of more than 10mg/day of prednisone
- Resting SpO2 <89% on 2 L nasal cannula continuous flow; unless at altitude > 4,000 feet, then resting oxygen saturation (SpO2) <89% on 4 L N C continuous flow
- Untreated arterial hypertension (systolic blood pressure greater than140 mm Hg, diastolic blood pressure greater than 90 mm Hg)
- Blood pressure less than 90 mm Hg systolic or 60 mm Hg diastolic while standing or sitting
- Known unilateral or bilateral renal artery stenosis higher than 70%
- Previous lung resection surgery
- Evidence of interstitial, occupational or chronic infectious lung disease
- Changes to chest that preclude adequate HRCT imaging (e.g. Metallic objects in the chest such as shrapnel or pacemaker leads)
- For women of child bearing potential, positive pregnancy test or unwillingness to use two methods of birth control or abstinence for the duration of the study
- Major chronic illnesses which in the judgment of the study physician would interfere with participation in the study e.g. including but not limited to: cardiac, renal, hepatic (LFTs more than 2.5x normal upper limit), neurological, psychiatric, endocrine or neoplastic diseases, uncontrolled diabetes, uncontrolled HIV infection or other immune system disorder, hyperthyroidism, seizure disorders, non-skin cancer, rheumatic diseases
- Failure to keep screening appointments or other indicators of non-adherence
- Inability to be contacted by telephone
- Intention to leave area within 12 months
Trial locations and contacts
28 sites in 1 country.
28 sites in 1 country
United States28 sites
University of Michigan
Ann Arbor, Michigan, 48109-5360
University of Alabama at Birmingham
Birmingham, Alabama, 35249
University of Illinois at Chicago
Chicago, Illinois, 60608
Northwestern University
Chicago, Illinois, 60611
Rush University Medical Center
Chicago, Illinois, 60612
University of Chicago Hospitals
Chicago, Illinois, 60637
Vermont Lung Center at The University of Vermont
Colchester, Vermont, 05466
Western Connecticut Health Network
Danbury, Connecticut, 06810
National Jewish Medical and Research Center
Denver, Colorado, 80206
Duke University Medical Center
Durham, North Carolina, 27710
Baylor College of Medicine
Houston, Texas, 77030
St. Vincent Hospital and Health Care Center, Inc.
Indianapolis, Indiana, 46260
University of Florida College of Medicine
Jacksonville, Florida, 32209
University of Kansas Medical Center
Kansas City, Kansas, 66160
Louisiana State University
New Orleans, Louisiana, 70112
New York University School of Medicine
New York, New York, 10016
Weill Cornell Medicine
New York, New York, 10021
Mount Sinai National Jewish Health Respiratory Institute; Icahn School of Medicine
New York, New York, 10029
Columbia University Medical Center
New York, New York, 10032
Temple University
Philadelphia, Pennsylvania, 19140
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
University of California at San Diego
San Diego, California, 92103
University of California at San Francisco
San Francisco, California, 94143
Pacific Northwest Airways - VA Puget Sound Healthcare System
Seattle, Washington, 98108
St. Louis University School of Medicine
St Louis, Missouri, 63104
St. Louis Asthma Clinical Research Center - Washington University School of Medicine
St Louis, Missouri, 63110
University of South Florida
Tampa, Florida, 33613
University of Arizona
Tucson, Arizona, 85724
About this study
A randomized, parallel, placebo controlled trial to evaluate the effect of 100mg/day losartan on the progression of emphysema as measured by quantitative HRCT compared to placebo
.
Read the detailed description
This is a trial designed to test if a treatment, losartan, may decrease the progression of Chronic Obstructive Pulmonary Disease (COPD). Losartan is an angiotensin receptor blocking agent, commonly used as an antihypertensive agent, which has been shown to alter cardiac remodeling after myocardial infarction and renovascular remodeling in diabetes-mellitus. In this trial participants with mild to severe COPD, with Computed Tomography (CT) evidence of emphysema (5-35% of voxels with < -950 Hounsfield Units), will be randomly assigned to receive 100mg/day of losartan or placebo for 48 weeks. The primary outcome measure will be the rate of progression of emphysema, quantified as the percent of lung voxels with a density less than -950 HU as measured by High Resolution CT (HRCT, from baseline to 48 weeks.
- Conditions
- Emphysema
- Being tested
- Losartan, Placebo
- Keywords
- COPD, emphysema, HRCT, losartan
- Medical subject headings
- Emphysema, Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LosartanDrug
50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated
PlaceboDrug
one capsule per day for two weeks, followed by two capsules per day for 46 weeks
| Study group | Role | What they receive |
|---|---|---|
| Losartan | Active comparator | At randomization participants will start with a dose of 50mg (one capsule) once a day for 2 weeks. If this dose is well tolerated and systolic BP is >90 mm Hg and diastolic BP is > 60 mm Hg, the dose will be increased to 100 mg (2 capsules) once a day for the remaining 46 weeks. Receives: Drug: Losartan |
| placebo | Placebo comparator | At randomization participants will start with a dose of one capsule (inactive) once a day for 2 weeks. After two weeks, if systolic BP is >90 mm Hg and diastolic BP is > 60 mm Hg, the dose will be increased to 2 capsules once a day for the remaining 46 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Mean pct950
change in percentage of voxels with density less than -950 Hounsfield Units
Measured: 48 weeks
Secondary outcomes (9)
Change From Baseline in Pre-bronchodilator FEV1 Percent Predicted
Change from the first visit to the final visit in a spirometry (breathing test) measure: forced expiratory volume in one second (FEV1). The test is administered without the participant taking any bronchodilator medication. The FEV1 is compared to standard predicted values in the US population for each individual based on their height, gender, and ethnic group; the result is given as percent of predicted value.
Measured: 48 weeks
Change From Baseline in Post-bronchodilator FEV1 Percent Predicted
Change from the first visit to the final visit in a spirometry (breathing test) measure: forced expiratory volume in one second (FEV1). This test is performed after the participant is given bronchodilator medications. The FEV1 is compared to standard predicted values in the US population for each individual based on their height, gender, and ethnic group; the result is given as percent of predicted value.
Measured: 48 weeks
Change From Baseline in CAT Score
Change from the first visit to the final visit in the participant's COPD Assessment Test (CAT) score. The CAT is an 8-item questionnaire assessing the impact of COPD on health status. CAT scores range from 0 to 40, with higher scores indicating a more severe impact of COPD on a patient's life.
Measured: 48 weeks
Change From Baseline in SGRQ Score: Total
Change from the first visit to the final visit in participants' score on the St George's Respiratory Questionnaire - COPD. The St George's Respiratory Questionnaire for COPD patients (SGRQ-C) is a 40-item questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with COPD. The SGRQ-C includes three categories: Symptoms (frequency and severity), Activities caused or limited by breathlessness, and Impacts on social and psychological functioning caused by airways disease. The total score and scores for each category range from 0 to 100, with higher scores indicating more limitations.
Measured: 48 weeks
Change From Baseline in SGRQ Score: Symptoms
Change from the first visit to the final visit in participants' scores on the symptom-related questions on the St Georges Respiratory Questionnaire-COPD. The St George's Respiratory Questionnaire for COPD patients (SGRQ-C) is a 40-item questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with COPD. The SGRQ-C includes three categories: Symptoms (frequency and severity), Activities caused or limited by breathlessness, and Impacts on social and psychological functioning caused by airways disease. The total score and scores for each category range from 0 to 100, with higher scores indicating more limitations.
Measured: 48 weeks
Change From Baseline in SGRQ Score: Activity
Change from the first visit to the final visit in participants' scores on the activity-related questions on the St Georges Respiratory Questionnaire-COPD. The St George's Respiratory Questionnaire for COPD patients (SGRQ-C) is a 40-item questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with COPD. The SGRQ-C includes three categories: Symptoms (frequency and severity), Activities caused or limited by breathlessness, and Impacts on social and psychological functioning caused by airways disease. The total score and scores for each category range from 0 to 100, with higher scores indicating more limitations.
Measured: 48 weeks
Change in SGRQ Score: Impact
Change from the first visit to the final visit in participants' scores on the impact-related questions on the St Georges Respiratory Questionnaire-COPD. The St George's Respiratory Questionnaire for COPD patients (SGRQ-C) is a 40-item questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with COPD. The SGRQ-C includes three categories: Symptoms (frequency and severity), Activities caused or limited by breathlessness, and Impacts on social and psychological functioning caused by airways disease. The total score and scores for each category range from 0 to 100, with higher scores indicating more limitations.
Measured: 48 weeks
Change From Baseline in mMRC Dyspnea Scale
Change from the first visit to the final visit in participants' scores on the modified Medical Research Council dyspnea scale. The modified Medical Research Council dyspnea scale (mMRC) is a self-rating tool to measure how much breathlessness affects someone's day to day activities. Scores are between 0 and 4, with higher scores indicating more severe breathlessness.
Measured: 48 weeks
Change From Baseline in PROMIS-20a T-score
Change from the first visit to the final visit in participants' scores on the Patient-Reported Outcome Measures Information System (PROMIS) Physical Function assessment. The Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form 20a is a 20-item questionnaire used to indicate a patient's ability to perform activities of daily living, such as bathing, dressing, and commuting. Raw scores from this questionnaire are compared to a reference population to create a "T-score". The general US population is the reference population. In this T-score metric, 50 indicates the population mean with a standard deviation of 10. Higher scores mean better outcomes (more ability to do activities of daily living)
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2016 (estimated)
- Study start23 May 2017
- Primary completion31 Mar 2021
- Study completion30 Jun 2021
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for EmphysemaStudies 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 220 participants (actual)
Sponsor and investigators
- Lead sponsor
- JHSPH Center for Clinical Trials
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pittsburgh
- Responsible party
- Sponsor
- Investigators
- Robert Wise, MD, Principal investigator, Johns Hopkins UniversityJanet Holbrook, PhD, Principal investigator, Johns Hopkins University Bloomberg School of Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02696564
- Sponsor's protocol ID
- U01HL128951
- Acronym
- LEEP
- Status last verified
- May 2022
- First submitted
- 25 Feb 2016
- Last updated
- 1 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC)
Publications
Wise RA, Holbrook JT, Brown RH, Criner GJ, Dransfield MT, He J, Henderson RJ, Kaminsky DA, Kaner RJ, Lazarus SC, Make BJ, McCormack MC, Neptune ER, Que LG. Clinical Trial of Losartan for Pulmonary Emphysema: Pulmonary Trials Cooperative Losartan Effects on Emphysema Progression Clinical Trial. Am J Respir Crit Care Med. 2022 Oct 1;206(7):838-845. doi: 10.1164/rccm.202201-0206OC.
PubMed 35649189
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Losartan Effects on Emphysema Progression
- ClinicalTrials.gov ID
- NCT02696564
- Acronym / sponsor ID
- LEEP / U01HL128951
- Conditions
- Emphysema
- Keywords
- COPD, emphysema, HRCT, losartan
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 220 participants (actual)
- Lead sponsor
- JHSPH Center for Clinical TrialsUniversity, hospital or other
- Collaborators
- University of Pittsburgh
- Study start
- 23 May 2017 (actual)
- Primary completion
- 31 Mar 2021 (actual)
- Study completion
- 30 Jun 2021 (actual)
- First posted
- 2 Mar 2016 (estimated)
- Results
- Posted 1 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomized, parallel, placebo controlled trial to evaluate the effect of 100mg/day losartan on the progression of emphysema as measured by quantitative HRCT compared to placebo
.
Detailed description
This is a trial designed to test if a treatment, losartan, may decrease the progression of Chronic Obstructive Pulmonary Disease (COPD). Losartan is an angiotensin receptor blocking agent, commonly used as an antihypertensive agent, which has been shown to alter cardiac remodeling after myocardial infarction and renovascular remodeling in diabetes-mellitus. In this trial participants with mild to severe COPD, with Computed Tomography (CT) evidence of emphysema (5-35% of voxels with < -950 Hounsfield Units), will be randomly assigned to receive 100mg/day of losartan or placebo for 48 weeks. The primary outcome measure will be the rate of progression of emphysema, quantified as the percent of lung voxels with a density less than -950 HU as measured by High Resolution CT (HRCT, from baseline to 48 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Losartan | Active comparator | Drug: LosartanAt randomization participants will start with a dose of 50mg (one capsule) once a day for 2 weeks. If this dose is well tolerated and systolic BP is >90 mm Hg and diastolic BP is > 60 mm Hg, the dose will be increased to 100 mg (2 capsules) once a day for the remaining 46 weeks. |
| placebo | Placebo comparator | Drug: PlaceboAt randomization participants will start with a dose of one capsule (inactive) once a day for 2 weeks. After two weeks, if systolic BP is >90 mm Hg and diastolic BP is > 60 mm Hg, the dose will be increased to 2 capsules once a day for the remaining 46 weeks. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Mild to severe COPD: Ratio of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) less than or equal to 0.70, FEV1 20-80% of predicted
- Current or former smoker
- HRCT scan with 5-35% of voxels with density less than -950 Hounsfield Units (HU)
- Ability to understand and willingness to sign consent documents
Key exclusion criteria (22 listed)
- Current therapy with angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)
- Known intolerance to ACE inhibitor or ARB
- History of angioedema
- Conventional indication for ACE inhibitor or ARB (e.g., history of myocardial infarction, known cardiomyopathy)
- Renal insufficiency (GFR <30 mL/min by Cockcroft-Gault calculation)
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 |
|---|---|---|
| Losartan50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated | Drug | Losartan |
| Placeboone capsule per day for two weeks, followed by two capsules per day for 46 weeks | Drug | placebo |
Primary outcome
Change in Mean pct950
Time frame: 48 weeks
change in percentage of voxels with density less than -950 Hounsfield Units
9 secondary outcomes
Change From Baseline in Pre-bronchodilator FEV1 Percent Predicted
Time frame: 48 weeks
Change From Baseline in Post-bronchodilator FEV1 Percent Predicted
Time frame: 48 weeks
Change From Baseline in CAT Score
Time frame: 48 weeks
Change From Baseline in SGRQ Score: Total
Time frame: 48 weeks
Change From Baseline in SGRQ Score: Symptoms
Time frame: 48 weeks
Change From Baseline in SGRQ Score: Activity
Time frame: 48 weeks
Change in SGRQ Score: Impact
Time frame: 48 weeks
Change From Baseline in mMRC Dyspnea Scale
Time frame: 48 weeks
Change From Baseline in PROMIS-20a T-score
Time frame: 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35649189Wise RA, Holbrook JT, Brown RH, Criner GJ, Dransfield MT, He J, Henderson RJ, Kaminsky DA, Kaner RJ, Lazarus SC, Make BJ, McCormack MC, Neptune ER, Que LG. Clinical Trial of Losartan for Pulmonary Emphysema: Pulmonary Trials Cooperative Losartan Effects on Emphysema Progression Clinical Trial. Am J Respir Crit Care Med. 2022 Oct 1;206(7):838-845. doi: 10.1164/rccm.202201-0206OC.
- Individual participant dataSharing planned: Yes. NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC)
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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.
Robert Wise, MD principal investigator
Johns Hopkins University
Janet Holbrook, PhD principal investigator
Johns Hopkins University Bloomberg School of Public Health
28 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 Losartan in people with Emphysema, run by JHSPH Center for Clinical Trials at 28 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 22 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 1 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 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 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?
Yes. Results are posted in the registry (first posted 1 Jun 2022). 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 Mean pct950 (time frame: 48 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 NCT02696564, which also lists 1 linked publication.
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 Jun 2022.