Anemia
Conditions
Brief summary
This study will assess the effect of anemia correction with NeoRecormon on cardiac structure and function in patients with early diabetic nephropathy. The anticipated time on study treatment is 1-2 years and the target sample size is 100-500 individuals.
Interventions
DRUGEpoetin beta
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* adult patients \>=18 years of age; * type 1 or type 2 diabetes; * stable glycemic control for \>=3 months; * diabetic nephropathy.
Exclusion criteria
* women who are pregnant, breastfeeding, or unwilling to use a reliable contraceptive method; * previous treatment with erythropoietin or other erythropoietic substance; * nondiabetic renal disease, nephrotic syndrome; * blood transfusion within the 3 months prior to enrollment; * administration of any investigational drug within 30 days preceding the study start, and during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Left Ventricle Mass Index (LVMI) at Month 15 | Baseline, Month 15 | LVMI (in g/m\^2) = (0.8 \[1.04 {(LVEDD + IVS + PWT)\^3 - (LVEDD)\^3}\] + 0.6) divided by BSA. Here, LVEDD = left ventricular end diastolic diameter (in centimeters \[cm\]); PWT = left ventricular posterior wall thickness in diastole (in cm); IVS = interventricular septal wall thickness in diastole (in cm). Echocardiogram was performed at baseline and Month 15 to interpret LVMI which was expressed in grams per meter square (g/m\^2). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular End Systolic Volume Index (LVESVI) | Baseline, Months 6 and 15 | LVESVI was calculated by dividing left ventricular end systolic volume (LVESV) (in milliliters \[mL\]) with body surface area (BSA) (in meter square \[m\^2\]). LVESVI is presented in milliliter per meter square (mL/m\^2). |
| Left Ventricular End Diastolic Volume Index (LVEDVI) | Baseline, Months 6 and 15 | LVEDVI was calculated by dividing left ventricular end diastolic volume (LVEDV) (in mL) BSA (in m\^2). LVEDVI was presented in mL/m\^2. |
| Fractional Myocardial Shortening (FS) | Baseline, Months 6 and 15 | FS was calculated as: (\[LVEDD - LVESD\] divided by LVEDV) multiplied by 100; where LVEDD = left ventricular end diastolic diameter (in centimeters \[cm\]), LVESD = left ventricular end systolic diameter (in cm), LVEDV = left ventricular end diastolic volume (in mL). FS is expressed in percentage of LVEDV. |
| Left Ventricular Ejection Fraction (LVEF) | Baseline, Months 6 and 15 | LVEF was calculated as (\[LVEDV - LVESV\], divided by LVEDV) multiplied by 100; where LVEDV = left ventricular end diastolic volume (in mL), LVESV = left ventricular end systolic volume (in mL). LVEF is expressed in percentage of LVEDV. |
| Percentage of Participants With Stable Hb Levels Between 13 to 15 g/dL | Week 26 up to Week 64 | — |
Countries
Austria, Brazil, Czechia, Denmark, Finland, Germany, Greece, Hungary, Italy, Mexico, Poland, Russia, Singapore, Spain, Sweden, Thailand, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 (Early Epoetin Beta) Along with their standard treatment participants received epoetin beta at a starting dose of 2000 IU SC once weekly to reach and maintain target Hb between 13 and 15 g/dL, for 15 months. Epoetin beta doses were adjusted according to individual participant's Hb level. Standard treatment was as per investigator discretion. | 88 |
| Group 2 (No/Late Epoetin Beta) Participants received their standard treatment for 15 months but no treatment for anemia correction unless Hb level was \<10.5 g/dL on 2 consecutive visits of 2 weeks interval or the Hb level was \<10 g/dL on a single determination. In such cases participants could receive epoetin beta at a starting dose of 2000 IU SC once weekly to reach and maintain a target Hb level of 10.5 to 11.5 g/dL. Standard treatment was as per investigator discretion. | 82 |
| Total | 170 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 0 | 2 |
| Overall Study | Failure to return | 0 | 1 |
| Overall Study | Other | 1 | 2 |
| Overall Study | Refused treatment | 1 | 2 |
Baseline characteristics
| Characteristic | Group 1 (Early Epoetin Beta) | Group 2 (No/Late Epoetin Beta) | Total |
|---|---|---|---|
| Age, Continuous | 56.7 years STANDARD_DEVIATION 13.82 | 55.6 years STANDARD_DEVIATION 12.64 | 56.2 years STANDARD_DEVIATION 13.24 |
| Sex: Female, Male Female | 43 Participants | 41 Participants | 84 Participants |
| Sex: Female, Male Male | 45 Participants | 41 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 88 | 17 / 82 |
| serious Total, serious adverse events | 21 / 88 | 20 / 82 |
Outcome results
Primary
Change From Baseline in Left Ventricle Mass Index (LVMI) at Month 15
LVMI (in g/m\^2) = (0.8 \[1.04 {(LVEDD + IVS + PWT)\^3 - (LVEDD)\^3}\] + 0.6) divided by BSA. Here, LVEDD = left ventricular end diastolic diameter (in centimeters \[cm\]); PWT = left ventricular posterior wall thickness in diastole (in cm); IVS = interventricular septal wall thickness in diastole (in cm). Echocardiogram was performed at baseline and Month 15 to interpret LVMI which was expressed in grams per meter square (g/m\^2).
Time frame: Baseline, Month 15
Population: ITT population. Here, number of participants analyzed = participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 (Early Epoetin Beta) | Change From Baseline in Left Ventricle Mass Index (LVMI) at Month 15 | 0.69 g/m^2 | Standard Deviation 26.34 |
| Group 2 (No/Late Epoetin Beta) | Change From Baseline in Left Ventricle Mass Index (LVMI) at Month 15 | 0.10 g/m^2 | Standard Deviation 24.25 |
p-value: 0.8811ANCOVA with LOCF
Secondary
Fractional Myocardial Shortening (FS)
FS was calculated as: (\[LVEDD - LVESD\] divided by LVEDV) multiplied by 100; where LVEDD = left ventricular end diastolic diameter (in centimeters \[cm\]), LVESD = left ventricular end systolic diameter (in cm), LVEDV = left ventricular end diastolic volume (in mL). FS is expressed in percentage of LVEDV.
Time frame: Baseline, Months 6 and 15
Population: ITT population. Here n= participants who were evaluable for each category, for respective arm groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (Early Epoetin Beta) | Fractional Myocardial Shortening (FS) | Baseline (n=88, 82) | 36.45 percentage of LVEDV | Standard Deviation 7.8 |
| Group 1 (Early Epoetin Beta) | Fractional Myocardial Shortening (FS) | Month 6 (n=84, 76) | 37.80 percentage of LVEDV | Standard Deviation 7.4 |
| Group 1 (Early Epoetin Beta) | Fractional Myocardial Shortening (FS) | Month 15 (n=85, 79) | 37.58 percentage of LVEDV | Standard Deviation 7.01 |
| Group 2 (No/Late Epoetin Beta) | Fractional Myocardial Shortening (FS) | Baseline (n=88, 82) | 36.58 percentage of LVEDV | Standard Deviation 8.97 |
| Group 2 (No/Late Epoetin Beta) | Fractional Myocardial Shortening (FS) | Month 6 (n=84, 76) | 38.49 percentage of LVEDV | Standard Deviation 7.03 |
| Group 2 (No/Late Epoetin Beta) | Fractional Myocardial Shortening (FS) | Month 15 (n=85, 79) | 38.86 percentage of LVEDV | Standard Deviation 7.52 |
p-value: 0.1578ANCOVA with LOCF
Secondary
Left Ventricular Ejection Fraction (LVEF)
LVEF was calculated as (\[LVEDV - LVESV\], divided by LVEDV) multiplied by 100; where LVEDV = left ventricular end diastolic volume (in mL), LVESV = left ventricular end systolic volume (in mL). LVEF is expressed in percentage of LVEDV.
Time frame: Baseline, Months 6 and 15
Population: ITT population. Here, number of participants analyzed = participants who were evaluable for this outcome measure. Here n= participants who were evaluable for each category, for respective arm groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (Early Epoetin Beta) | Left Ventricular Ejection Fraction (LVEF) | Baseline (n=57, 56) | 63.44 percentage of LVEDV | Standard Deviation 5.73 |
| Group 1 (Early Epoetin Beta) | Left Ventricular Ejection Fraction (LVEF) | Month 6 (n=47, 53) | 57.22 percentage of LVEDV | Standard Deviation 6.87 |
| Group 1 (Early Epoetin Beta) | Left Ventricular Ejection Fraction (LVEF) | Month 15 (n=54, 55) | 58.63 percentage of LVEDV | Standard Deviation 6.47 |
| Group 2 (No/Late Epoetin Beta) | Left Ventricular Ejection Fraction (LVEF) | Baseline (n=57, 56) | 63.84 percentage of LVEDV | Standard Deviation 5.44 |
| Group 2 (No/Late Epoetin Beta) | Left Ventricular Ejection Fraction (LVEF) | Month 6 (n=47, 53) | 59.92 percentage of LVEDV | Standard Deviation 7.71 |
| Group 2 (No/Late Epoetin Beta) | Left Ventricular Ejection Fraction (LVEF) | Month 15 (n=54, 55) | 59.97 percentage of LVEDV | Standard Deviation 6.46 |
p-value: 0.2913ANCOVA with LOCF
Secondary
Left Ventricular End Diastolic Volume Index (LVEDVI)
LVEDVI was calculated by dividing left ventricular end diastolic volume (LVEDV) (in mL) BSA (in m\^2). LVEDVI was presented in mL/m\^2.
Time frame: Baseline, Months 6 and 15
Population: ITT population. Here, number of participants analyzed = participants who were evaluable for this outcome measure. Here n= participants who were evaluable for each category, for respective arm groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (Early Epoetin Beta) | Left Ventricular End Diastolic Volume Index (LVEDVI) | Baseline (n=57, 56) | 61.08 mL/m^2 | Standard Deviation 12.69 |
| Group 1 (Early Epoetin Beta) | Left Ventricular End Diastolic Volume Index (LVEDVI) | Month 6 (n=47, 53) | 62.74 mL/m^2 | Standard Deviation 15.41 |
| Group 1 (Early Epoetin Beta) | Left Ventricular End Diastolic Volume Index (LVEDVI) | Month 15 (n=54, 55) | 62.26 mL/m^2 | Standard Deviation 16.27 |
| Group 2 (No/Late Epoetin Beta) | Left Ventricular End Diastolic Volume Index (LVEDVI) | Month 15 (n=54, 55) | 62.07 mL/m^2 | Standard Deviation 11.36 |
| Group 2 (No/Late Epoetin Beta) | Left Ventricular End Diastolic Volume Index (LVEDVI) | Baseline (n=57, 56) | 58.13 mL/m^2 | Standard Deviation 10.83 |
| Group 2 (No/Late Epoetin Beta) | Left Ventricular End Diastolic Volume Index (LVEDVI) | Month 6 (n=47, 53) | 60.40 mL/m^2 | Standard Deviation 12.25 |
p-value: 0.5681ANCOVA with LOCF
Secondary
Left Ventricular End Systolic Volume Index (LVESVI)
LVESVI was calculated by dividing left ventricular end systolic volume (LVESV) (in milliliters \[mL\]) with body surface area (BSA) (in meter square \[m\^2\]). LVESVI is presented in milliliter per meter square (mL/m\^2).
Time frame: Baseline, Months 6 and 15
Population: ITT population. Here, number of participants analyzed = participants who were evaluable for this outcome measure. Here n= participants who were evaluable for each category, for respective arm groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (Early Epoetin Beta) | Left Ventricular End Systolic Volume Index (LVESVI) | Baseline (n=57, 56) | 22.40 mL/m^2 | Standard Deviation 6.36 |
| Group 1 (Early Epoetin Beta) | Left Ventricular End Systolic Volume Index (LVESVI) | Month 6 (n=47, 53) | 26.86 mL/m^2 | Standard Deviation 8.21 |
| Group 1 (Early Epoetin Beta) | Left Ventricular End Systolic Volume Index (LVESVI) | Month 15 (n=54, 55) | 25.99 mL/m^2 | Standard Deviation 9.31 |
| Group 2 (No/Late Epoetin Beta) | Left Ventricular End Systolic Volume Index (LVESVI) | Baseline (n=57, 56) | 21.04 mL/m^2 | Standard Deviation 5.42 |
| Group 2 (No/Late Epoetin Beta) | Left Ventricular End Systolic Volume Index (LVESVI) | Month 6 (n=47, 53) | 24.54 mL/m^2 | Standard Deviation 8.06 |
| Group 2 (No/Late Epoetin Beta) | Left Ventricular End Systolic Volume Index (LVESVI) | Month 15 (n=54, 55) | 25.03 mL/m^2 | Standard Deviation 6.88 |
p-value: 0.8864ANCOVA with LOCF
Secondary
Percentage of Participants With Stable Hb Levels Between 13 to 15 g/dL
Time frame: Week 26 up to Week 64
Population: ITT population. Here, number of participants analyzed = participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (Early Epoetin Beta) | Percentage of Participants With Stable Hb Levels Between 13 to 15 g/dL | 75.6 percentage of participants |
| Group 2 (No/Late Epoetin Beta) | Percentage of Participants With Stable Hb Levels Between 13 to 15 g/dL | 9.9 percentage of participants |
p-value: <0.001Chi-squared, Corrected