Heart Failure
Conditions
Brief summary
This is a multicenter study to evaluate potential decrease in hospitalization events and time between events and increasing longevity in patients with symptomatic congestive heart failure and intolerant of first-line medication for heart failure. This study will evaluate if higher doses of the investigational drug given daily will be superior to the lower dose of the same investigational drug given daily.
Interventions
DRUGLosartan 150 mg
100-mg losartan oral tablet + 50-mg losartan oral tablet
DRUGLosartan 50 mg
50-mg losartan oral tablet
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Symptomatic heart failure with known or recently diagnosed intolerance of treatment with first-line medication for heart failure * May or may not be receiving an alternative and/or additional drug treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants That Experienced One Component of the Composite Clinical Endpoint of All Cause Death or Hospitalization for Heart Failure | Entire follow-up (median = 4.7 years) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Experienced One Components of the Composite Clinical Endpoint of All Cause Death or Cardiovascular Hospitalization | Entire follow-up (median = 4.7 years) | Cardiovascular hospitalization is defined as any hospitalization that may be attributed to a cardiovascular cause, including heart failure. |
| Number of Participants That Died (Any Cause) | Entire follow-up (median = 4.7 years) | — |
| Number of Participants That Were Hospitalized for Heart Failure | Entire follow-up (median = 4.7 years) | — |
| Number of Participants That Experienced Cardiovascular Hospitalization | Entire follow-up (median = 4.7 years) | — |
Participant flow
Recruitment details
First patient in: Nov-2001. Last patient out: May-2009. 255 sites in 30 countries participated (Peru , Chile, Columbia, Mexico, Brazil, Belgium, Croatia, France, Germany, Greece, Holland, Italy, Norway, Poland, Russia, Slovenia, Spain, Turkey, UK, Egypt, Lebanon, Morocco, S. Africa, China, Hong Kong, Korea, Malaysia, Philippines, Singapore, Taiwan)
Pre-assignment details
Patients who were on a Angiotensin II Antagonist (AIIA) had the option to begin losartan treatment with open-label losartan 12.5 mg for one week followed by losartan 25 mg for one week and were subsequently randomized to losartan 50 mg or losartan 150 mg.
Participants by arm
| Arm | Count |
|---|---|
| Losartan 50 mg | 1,913 |
| Losartan 150 mg | 1,921 |
| Total | 3,834 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Investigator site closed | 11 | 7 |
| Overall Study | Lost to Follow-up | 30 | 26 |
| Overall Study | Withdrawal by Subject | 21 | 15 |
Baseline characteristics
| Characteristic | Losartan 50 mg | Losartan 150 mg | Total |
|---|---|---|---|
| Age, Continuous | 64.1 years | 64.4 years | 64.2 years |
| Age, Customized < 65 years of Age | 889 participants | 879 participants | 1768 participants |
| Age, Customized >=65 years of Age | 1024 participants | 1042 participants | 2066 participants |
| Angiotensin II antagonists No | 456 Participants | 438 Participants | 894 Participants |
| Angiotensin II antagonists Yes | 1457 Participants | 1483 Participants | 2940 Participants |
| New York Heart Association (NYHA) functional status III Marked limitation | 569 Participants | 583 Participants | 1152 Participants |
| New York Heart Association (NYHA) functional status II Mild symptoms | 1330 Participants | 1327 Participants | 2657 Participants |
| New York Heart Association (NYHA) functional status I No symptoms | 2 Participants | 1 Participants | 3 Participants |
| New York Heart Association (NYHA) functional status IV Severe limitations | 12 Participants | 10 Participants | 22 Participants |
| Region Asia and Pacific Region | 391 participants | 390 participants | 781 participants |
| Region East Europe | 212 participants | 207 participants | 419 participants |
| Region Latin America | 309 participants | 315 participants | 624 participants |
| Region Middle East and Africa | 97 participants | 97 participants | 194 participants |
| Region West Europe | 904 participants | 912 participants | 1816 participants |
| Sex: Female, Male Female | 560 Participants | 583 Participants | 1143 Participants |
| Sex: Female, Male Male | 1353 Participants | 1338 Participants | 2691 Participants |
| β - Blocker therapy No | 543 Participants | 533 Participants | 1076 Participants |
| β - Blocker therapy Yes | 1370 Participants | 1388 Participants | 2758 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1,358 / 1,913 | 1,394 / 1,921 |
| serious Total, serious adverse events | 691 / 1,913 | 710 / 1,921 |
Outcome results
Primary
Number of Participants That Experienced One Component of the Composite Clinical Endpoint of All Cause Death or Hospitalization for Heart Failure
Time frame: Entire follow-up (median = 4.7 years)
Population: Intention-to-Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Losartan 50 mg | Number of Participants That Experienced One Component of the Composite Clinical Endpoint of All Cause Death or Hospitalization for Heart Failure | 889 Participants |
| Losartan 150 mg | Number of Participants That Experienced One Component of the Composite Clinical Endpoint of All Cause Death or Hospitalization for Heart Failure | 828 Participants |
p-value: 0.02795% CI: [0.818, 0.988]Regression, Cox
Secondary
Number of Participants That Died (Any Cause)
Time frame: Entire follow-up (median = 4.7 years)
Population: Intention-to-Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Losartan 50 mg | Number of Participants That Died (Any Cause) | 665 Participants |
| Losartan 150 mg | Number of Participants That Died (Any Cause) | 635 Participants |
p-value: 0.23595% CI: [0.84, 1.044]Regression, Cox
Secondary
Number of Participants That Experienced Cardiovascular Hospitalization
Time frame: Entire follow-up (median = 4.7 years)
Population: Intention-to-Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Losartan 50 mg | Number of Participants That Experienced Cardiovascular Hospitalization | 826 Participants |
| Losartan 150 mg | Number of Participants That Experienced Cardiovascular Hospitalization | 762 Participants |
p-value: 0.02395% CI: [0.808, 0.984]Regression, Cox
Secondary
Number of Participants That Experienced One Components of the Composite Clinical Endpoint of All Cause Death or Cardiovascular Hospitalization
Cardiovascular hospitalization is defined as any hospitalization that may be attributed to a cardiovascular cause, including heart failure.
Time frame: Entire follow-up (median = 4.7 years)
Population: Intention-to-Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Losartan 50 mg | Number of Participants That Experienced One Components of the Composite Clinical Endpoint of All Cause Death or Cardiovascular Hospitalization | 1085 Participants |
| Losartan 150 mg | Number of Participants That Experienced One Components of the Composite Clinical Endpoint of All Cause Death or Cardiovascular Hospitalization | 1037 Participants |
p-value: 0.06895% CI: [0.848, 1.006]Regression, Cox
Secondary
Number of Participants That Were Hospitalized for Heart Failure
Time frame: Entire follow-up (median = 4.7 years)
Population: Intention-to-Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Losartan 50 mg | Number of Participants That Were Hospitalized for Heart Failure | 503 Participants |
| Losartan 150 mg | Number of Participants That Were Hospitalized for Heart Failure | 450 Participants |
p-value: 0.02595% CI: [0.762, 0.982]Regression, Cox