Losartan Effects on Emphysema Progression | NCT02696564

Obsolete or Duplicate NCT IDs

Not provided

Status Module

Sponsor/Collaborators Module

Name	Class
University of Pittsburgh	OTHER

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.	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.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Losartan	Drug	50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated	Losartan

Outcomes Module

Measure	Description	Time Frame
Change in Mean pct950	change in percentage of voxels with density less than -950 Hounsfield Units	48 weeks

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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
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

Contacts/Locations Module

Name	Affiliation	Role
Robert Wise, MD	Johns Hopkins University	Principal Investigator
Janet Holbrook, PhD	Johns Hopkins University Bloomberg School of Public Health	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35249	United States
University of Arizona

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
35649189	Derived	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.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Losartan	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. Losartan: 50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	May 17, 2018

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Losartan	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. Losartan: 50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated
BG001	Placebo	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. Placebo: one capsule per day for two weeks, followed by two capsules per day for 46 weeks
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Inter-Quartile Range

years

Title

Denominators

Categories

Title	Measurements
	OG0001.35(0.67 to 2.02) OG0010.66(0.09 to 1.23)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis	P-value based on generalized linear mixed models with covariates for site, baseline value, and for treatment group.	0.133														Superiority	We will estimate a 95% confidence interval for the losartan vs placebo mean difference, using the regression estimate and the t-distribution; we will reject the null that losartan is equivalent to placebo if the 95% interval excludes 0.0.

Secondary

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.

Pre-bronchodilator results were not available at the baseline and/or final visit for 57 participants in the Losartan group and 56 participants in the placebo group. This was due in part to the elimination of all non-medically necessary spirometry testing during the COVID-19 pandemic.

Posted

Least Squares Mean

95% Confidence Interval

percentage of predicted value

48 weeks

ID	Title	Description
OG000	Losartan	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. Losartan: 50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated
OG001	Placebo	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. Placebo: one capsule per day for two weeks, followed by two capsules per day for 46 weeks

Secondary

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.

Post-bronchodilator results were not available at the baseline and/or final visit for 35 participants in the Losartan group and 39 participants in the placebo group. This was due in part to the elimination of all non-medically necessary spirometry testing during the COVID-19 pandemic.

Posted

Least Squares Mean

95% Confidence Interval

percentage of predicted value

48 weeks

ID	Title	Description
OG000	Losartan	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. Losartan: 50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated
OG001	Placebo	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. Placebo: one capsule per day for two weeks, followed by two capsules per day for 46 weeks

Secondary

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.

CAT results were not available at the baseline and/or final visit for 9 participants in the Losartan group and 8 participants in the placebo group.

Posted

Least Squares Mean

95% Confidence Interval

score on a scale

48 weeks

ID	Title	Description
OG000	Losartan	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. Losartan: 50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated
OG001	Placebo	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. Placebo: one capsule per day for two weeks, followed by two capsules per day for 46 weeks

Secondary

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.

Total SGRQ results were not available at the baseline and/or final visit for 9 participants in the Losartan group and 9 participants in the placebo group.

Posted

Least Squares Mean

95% Confidence Interval

score on a scale

48 weeks

ID	Title	Description
OG000	Losartan	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. Losartan: 50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated
OG001	Placebo	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. Placebo: one capsule per day for two weeks, followed by two capsules per day for 46 weeks

Secondary

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.

SGRQ results were not available at the baseline and/or final visit for 9 participants in the Losartan group and 9 participants in the placebo group.

Posted

Least Squares Mean

95% Confidence Interval

score on a scale

48 weeks

ID	Title	Description
OG000	Losartan	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. Losartan: 50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated
OG001	Placebo	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. Placebo: one capsule per day for two weeks, followed by two capsules per day for 46 weeks

Secondary

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.

SGRQ results were not available at the baseline and/or final visit for 9 participants in the Losartan group and 9 participants in the placebo group.

Posted

Least Squares Mean

95% Confidence Interval

score on a scale

48 weeks

ID	Title	Description
OG000	Losartan	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. Losartan: 50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated
OG001	Placebo	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. Placebo: one capsule per day for two weeks, followed by two capsules per day for 46 weeks

Secondary

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.

SGRQ results were not available at the baseline and/or final visit for 9 participants in the Losartan group and 9 participants in the placebo group.

Posted

Least Squares Mean

95% Confidence Interval

score on a scale

48 weeks

ID	Title	Description
OG000	Losartan	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. Losartan: 50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated
OG001	Placebo	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. Placebo: one capsule per day for two weeks, followed by two capsules per day for 46 weeks

Secondary

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.

mMRC dyspnea scale results were not available at the baseline and/or final visit for 9 participants in the Losartan group and 9 participants in the placebo group.

Posted

Least Squares Mean

95% Confidence Interval

score on a scale

48 weeks

ID	Title	Description
OG000	Losartan	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. Losartan: 50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated
OG001	Placebo	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. Placebo: one capsule per day for two weeks, followed by two capsules per day for 46 weeks

Secondary

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)

PROMIS-20a results were not available at the baseline and/or final visit for 9 participants in the Losartan group and 10 participants in the placebo group.

Posted

Least Squares Mean

95% Confidence Interval

score on a scale

48 weeks

ID	Title	Description
OG000	Losartan	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. Losartan: 50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated
OG001	Placebo

Post-Hoc

Number of COPD Exacerbations by Severity and Treatment Assignment

This measure assessed the number of exacerbations of chronic obstructive pulmonary disease in both the losartan and placebo treatment groups. Participants were asked about current and past exacerbations during each study visit. Exacerbations were defined as 2 or more worsening COPD symptoms lasting 3 or more consecutive days that required a new prescribed treatment. Each exacerbation was further classified as "mild" (requiring only a change in existing COPD medications),"moderate" (requiring a new prescription for a steroid and/or antibiotic), or "severe" (requiring a hospitalization for COPD symptoms).

The analysis population consists of the number of participants who reported at least one exacerbation in each treatment group. Two participants in the losartan treatment group did not report any COPD exacerbations during the study.

Posted

Number

exacerbation events

48 weeks

ID	Title	Description
OG000	Losartan	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. Losartan: 50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated
OG001	Placebo	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. Placebo: one capsule per day for two weeks, followed by two capsules per day for 46 weeks

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Losartan	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. Losartan: 50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated	1	108	18	108	106	108
EG001	Placebo	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. Placebo: one capsule per day for two weeks, followed by two capsules per day for 46 weeks	2	112	25	112	112	112

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
COPD Exacerbation	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0006 events6 affected108 at risk EG00119 events15 affected112 at risk
Bronchitis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected112 at risk
Pneumonia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected108 at risk EG0013 events3 affected112 at risk
Acute respiratory failure secondary to end stage COPD	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected108 at risk EG0011 events1 affected112 at risk
Collapsed lung	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected112 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected112 at risk
Radiation pneumonitis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected112 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected112 at risk
Hypercapnic respiratory failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected112 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected112 at risk
Shortness of breath	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected112 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected112 at risk
Lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0002 events2 affected108 at risk EG0010 events0 affected112 at risk
Lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected112 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected112 at risk
Myocardial infarction	Cardiac disorders	Systematic Assessment	EG0001 events1 affected108 at risk EG0011 events1 affected112 at risk
Coronary artery disease	Cardiac disorders	Systematic Assessment	EG0000 events0 affected108 at risk EG0013 events3 affected112 at risk
Total knee replacement	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected112 at risk
Spinal fusion revision	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected112 at risk
Falls	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected112 at risk
Ankle fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected112 at risk
Motor vehicle accident	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected112 at risk
Influenza	Infections and infestations	Systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected112 at risk
Sepsis	Infections and infestations	Systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected112 at risk
Gastrointestinal bleeding	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected108 at risk EG0012 events2 affected112 at risk
Dehydration	General disorders	Systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected112 at risk
Vertigo	Ear and labyrinth disorders	Systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected112 at risk
Near syncope	Nervous system disorders	Systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected112 at risk
Pseudogout	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected112 at risk
Panic attack	Psychiatric disorders	Systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected112 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Chest pain	Cardiac disorders	Systematic Assessment	EG00010 events9 affected108 at risk EG0019 events8 affected112 at risk
Edema	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0009 events8 affected108 at risk EG00115 events10 affected112 at risk
Skin rash or hives	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0009 events9 affected108 at risk EG0019 events7 affected112 at risk
Diarrhea	Gastrointestinal disorders	Systematic Assessment	EG00015 events13 affected108 at risk EG00116 events12 affected112 at risk
Heartburn/indigestion	Gastrointestinal disorders	Systematic Assessment	EG00017 events11 affected108 at risk EG00136 events24 affected112 at risk
Nausea/vomiting	Gastrointestinal disorders	Systematic Assessment	EG0007 events7 affected108 at risk EG00111 events10 affected112 at risk
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG00057 events33 affected108 at risk EG00177 events38 affected112 at risk
Muscle cramps	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG00046 events28 affected108 at risk EG00149 events30 affected112 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG00050 events30 affected108 at risk EG00163 events32 affected112 at risk
Weakness	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG00036 events19 affected108 at risk EG00136 events24 affected112 at risk
Dizziness/lightheadedness	Nervous system disorders	Systematic Assessment	EG00034 events27 affected108 at risk EG00120 events16 affected112 at risk
Headache/ head pain	Nervous system disorders	Systematic Assessment	EG00038 events26 affected108 at risk EG00152 events35 affected112 at risk
Fatigue	General disorders	Systematic Assessment	EG00071 events38 affected108 at risk EG00177 events41 affected112 at risk
Fever	General disorders	Systematic Assessment	EG0005 events5 affected108 at risk EG0016 events6 affected112 at risk
Sleep problems	General disorders	Systematic Assessment	EG00046 events30 affected108 at risk EG00165 events34 affected112 at risk
Sore throat	General disorders	Systematic Assessment	EG0009 events8 affected108 at risk EG00124 events18 affected112 at risk
Congestion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00073 events42 affected108 at risk EG00170 events47 affected112 at risk
Dry cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00026 events22 affected108 at risk EG00157 events34 affected112 at risk
Mild COPD exacerbation	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0003 events3 affected108 at risk EG0014 events4 affected112 at risk
Moderate COPD exacerbation	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00041 events25 affected108 at risk EG00147 events29 affected112 at risk
Severe COPD exacerbation	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0007 events7 affected108 at risk EG00121 events14 affected112 at risk

First MCP Posted Date

ID	Term
D004646	Emphysema
D029424	Pulmonary Disease, Chronic Obstructive

Ancestor Terms

ID	Term
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002908	Chronic Disease
D020969	Disease Attributes

ID	Term
D019808	Losartan

Ancestor Terms

ID	Term
D001713	Biphenyl Compounds
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D007093	Imidazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D013777	Tetrazoles

ParticipantsBG002220

Units	Counts
Participants	OG00099 OG001104

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.

Placebo: one capsule per day for two weeks, followed by two capsules per day for 46 weeks