Extended epoetin alfa dosing as maintenance treatment for the anemia of chronic kidney disease: The PROMPT study

Robert Provenzano, S. Bhaduri, A. K. Singh, M. Abrante, D. Chang, Y. H. Lien, J. Chandrashekar, M. Dana, S. Friedman, K. Kleinman, V. Kondle, R. A. Lafayette, H. Madkour, D. Makoff, R. L. Mehta, D. Ricker, M. Samson, M. Shapiro, M. Spira, C. SunK. Tucker, M. Esson, K. D. Caanthan, J. Cohen, R. Geronemus, D. Hoffman, H. Locay, M. McIvor, J. Navarro, E. Pellegrini, G. Ramirez, D. Rowe, G. Serrano, M. Vacker, R. Weiss, S. Zeig, J. Bazemore, E. Frederickson, E. Himot, C. Martinez, S. Murphy, K. Nass, C. Obialo, S. Vainer, R. Bilinsky, C. Ghossein, M. Kamran, D. J. Leehey, R. Sparrow, Sharon Karp, Tim Taber, M. Kaskas, R. Zabaneh, S. Hood, G. Kershaw, P. Lazowski, D. Shih, J. Slater, K. K. Al-Talib, J. Fink, P. Turer, M. Wassem, F. Al-Saghir, V. Rao, A. Awad, D. Domoto, J. Mellas, K. Brandspigel, L. Spry, B. Eidelson, J. Feldman, A. Haratz, M. Huq, L. Lehrner, M. Leisrowitz, L. Shete, M. Henriquez, C. Hoy, L. Mailloux, I. J. Miller, E. Parnes, D. Scott, J. Wagner, L. H. Cohen, V. W. Dennis, K. S. Kant, D. K. Malhotra, B. von Hartitzsch, T. M. Kennefick, R. L. Benz, E. Clark, E. Filippone, F. Foti, Y. B. Kurtzer, D. Levenson, H. Raza, C. Rodenberger, M. Rudnick, M. A. Testa

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Aim: To determine whether extended epoetin alfa dosing schedules of up to once every four weeks are as effective as weekly dosing in maintaining hemoglobin (Hb) levels in patients with anemia of chronic kidney disease (CKD). Methods: This randomized, open-label trial enrolled patients with anemia of CKD not on dialysis. Patients were required to have a stable Hb level (≥ 11.0 g/dl) and to have been previously receiving epoetin alfa for two or more months. Patients were randomized to one of four subcutaneously administered epoetin alfa dosing regimens: 10,000 units (U) once weekly (QW), 20,000 U every two weeks (Q2W), 30,000 U every three weeks (Q3W) or 40,000 U every four weeks (Q4W). Dose reductions, but not escalations, were permitted. Patients received treatment for a total of 16 weeks. The primary endpoint for the trial was the mean final Hb measurements of the QW, Q2W, Q3W, and Q4W groups. The primary efficacy analyses were non-inferiority assessments of the mean final Hb measurements of the Q2W, Q3W, and Q4W groups, compared with the QW group. The primary efficacy analyses were performed using a modified intent-to-treat (MITT) population, defined as all patients meeting all inclusion/exclusion criteria (or, if not satisfying all criteria, were granted an exemption at study entry), and who were randomized and received at least one dose of study medication. A per-protocol population, based on all patients who met the MITT criteria and completed the entire study, was used to evaluate the robustness of the MITT results. Quality of life was assessed for all dosing groups throughout the study. Safety was based on all patients randomized who received at least one dose of study medication. Results: A total of 519 patients were enrolled; 445 were included in the MITT population. The four treatment groups were comparable with respect to baseline characteristics. The primary etiologies of CKD were diabetes (45.7%) and hypertension (29.9%). The mean baseline Hb, serum creatinine and glomerular filtration rate for all patients were 11.9 ± 0.8 g/dl, 3.1 mg/dl, and 21.1 ml/min/1.73 m2, respectively. The mean baseline transferrin saturation was 25.2% and the mean ferritin was 201.9 ng/ml for all patients. All groups had a mean final Hb of > 11.0 g/dl. The mean final Hb levels of the Q2W and Q4W groups were statistically non-inferior to the QW group. The results of the per-protocol analysis were consistent with the MITT results. In addition, 93.5%, 89.5%, 77.2%, and 76.0% of patients maintained a mean Hb ≥ 11.0 g/dl throughout the course of the study in the QW, Q2W, Q3W, and Q4W groups, respectively. Quality of life was maintained or improved from baseline to final within each dosing group. There were no significant differences in the mean final quality of life scores between the QW group and the Q2W, Q3W, and Q4W groups. Among the 513 patients evaluated for safety, epoetin alfa was well tolerated with no differences in adverse events between groups. The incidence of thrombotic adverse events was low (2.5% of patients), as was mortality (1.4% of patients). Conclusions: Approximately 90% of patients dosed once every two weeks and over 75% of patients dosed once every three or four weeks maintained mean Hb levels ≥ 11.0 g/dl, consistent with the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. This study suggests that extended epoetin alfa dosing schedules are effective and safe for maintaining Hb, and may offer the possibility of increased flexibility and convenience for the majority of patients with the anemia of CKD.

Original languageEnglish (US)
Pages (from-to)113-123
Number of pages11
JournalClinical Nephrology
Volume64
Issue number2
StatePublished - Aug 2005
Externally publishedYes

Fingerprint

Epoetin Alfa
Chronic Renal Insufficiency
Anemia
Hemoglobins
Therapeutics
Quality of Life

Keywords

  • Anemia
  • Chronic kidney disease
  • Epoetin alfa
  • Hemoglobin

ASJC Scopus subject areas

  • Nephrology

Cite this

Provenzano, R., Bhaduri, S., Singh, A. K., Abrante, M., Chang, D., Lien, Y. H., ... Testa, M. A. (2005). Extended epoetin alfa dosing as maintenance treatment for the anemia of chronic kidney disease: The PROMPT study. Clinical Nephrology, 64(2), 113-123.

Extended epoetin alfa dosing as maintenance treatment for the anemia of chronic kidney disease : The PROMPT study. / Provenzano, Robert; Bhaduri, S.; Singh, A. K.; Abrante, M.; Chang, D.; Lien, Y. H.; Chandrashekar, J.; Dana, M.; Friedman, S.; Kleinman, K.; Kondle, V.; Lafayette, R. A.; Madkour, H.; Makoff, D.; Mehta, R. L.; Ricker, D.; Samson, M.; Shapiro, M.; Spira, M.; Sun, C.; Tucker, K.; Esson, M.; Caanthan, K. D.; Cohen, J.; Geronemus, R.; Hoffman, D.; Locay, H.; McIvor, M.; Navarro, J.; Pellegrini, E.; Ramirez, G.; Rowe, D.; Serrano, G.; Vacker, M.; Weiss, R.; Zeig, S.; Bazemore, J.; Frederickson, E.; Himot, E.; Martinez, C.; Murphy, S.; Nass, K.; Obialo, C.; Vainer, S.; Bilinsky, R.; Ghossein, C.; Kamran, M.; Leehey, D. J.; Sparrow, R.; Karp, Sharon; Taber, Tim; Kaskas, M.; Zabaneh, R.; Hood, S.; Kershaw, G.; Lazowski, P.; Shih, D.; Slater, J.; Al-Talib, K. K.; Fink, J.; Turer, P.; Wassem, M.; Al-Saghir, F.; Rao, V.; Awad, A.; Domoto, D.; Mellas, J.; Brandspigel, K.; Spry, L.; Eidelson, B.; Feldman, J.; Haratz, A.; Huq, M.; Lehrner, L.; Leisrowitz, M.; Shete, L.; Henriquez, M.; Hoy, C.; Mailloux, L.; Miller, I. J.; Parnes, E.; Scott, D.; Wagner, J.; Cohen, L. H.; Dennis, V. W.; Kant, K. S.; Malhotra, D. K.; von Hartitzsch, B.; Kennefick, T. M.; Benz, R. L.; Clark, E.; Filippone, E.; Foti, F.; Kurtzer, Y. B.; Levenson, D.; Raza, H.; Rodenberger, C.; Rudnick, M.; Testa, M. A.

In: Clinical Nephrology, Vol. 64, No. 2, 08.2005, p. 113-123.

Research output: Contribution to journalArticle

Provenzano, R, Bhaduri, S, Singh, AK, Abrante, M, Chang, D, Lien, YH, Chandrashekar, J, Dana, M, Friedman, S, Kleinman, K, Kondle, V, Lafayette, RA, Madkour, H, Makoff, D, Mehta, RL, Ricker, D, Samson, M, Shapiro, M, Spira, M, Sun, C, Tucker, K, Esson, M, Caanthan, KD, Cohen, J, Geronemus, R, Hoffman, D, Locay, H, McIvor, M, Navarro, J, Pellegrini, E, Ramirez, G, Rowe, D, Serrano, G, Vacker, M, Weiss, R, Zeig, S, Bazemore, J, Frederickson, E, Himot, E, Martinez, C, Murphy, S, Nass, K, Obialo, C, Vainer, S, Bilinsky, R, Ghossein, C, Kamran, M, Leehey, DJ, Sparrow, R, Karp, S, Taber, T, Kaskas, M, Zabaneh, R, Hood, S, Kershaw, G, Lazowski, P, Shih, D, Slater, J, Al-Talib, KK, Fink, J, Turer, P, Wassem, M, Al-Saghir, F, Rao, V, Awad, A, Domoto, D, Mellas, J, Brandspigel, K, Spry, L, Eidelson, B, Feldman, J, Haratz, A, Huq, M, Lehrner, L, Leisrowitz, M, Shete, L, Henriquez, M, Hoy, C, Mailloux, L, Miller, IJ, Parnes, E, Scott, D, Wagner, J, Cohen, LH, Dennis, VW, Kant, KS, Malhotra, DK, von Hartitzsch, B, Kennefick, TM, Benz, RL, Clark, E, Filippone, E, Foti, F, Kurtzer, YB, Levenson, D, Raza, H, Rodenberger, C, Rudnick, M & Testa, MA 2005, 'Extended epoetin alfa dosing as maintenance treatment for the anemia of chronic kidney disease: The PROMPT study', Clinical Nephrology, vol. 64, no. 2, pp. 113-123.
Provenzano R, Bhaduri S, Singh AK, Abrante M, Chang D, Lien YH et al. Extended epoetin alfa dosing as maintenance treatment for the anemia of chronic kidney disease: The PROMPT study. Clinical Nephrology. 2005 Aug;64(2):113-123.
Provenzano, Robert ; Bhaduri, S. ; Singh, A. K. ; Abrante, M. ; Chang, D. ; Lien, Y. H. ; Chandrashekar, J. ; Dana, M. ; Friedman, S. ; Kleinman, K. ; Kondle, V. ; Lafayette, R. A. ; Madkour, H. ; Makoff, D. ; Mehta, R. L. ; Ricker, D. ; Samson, M. ; Shapiro, M. ; Spira, M. ; Sun, C. ; Tucker, K. ; Esson, M. ; Caanthan, K. D. ; Cohen, J. ; Geronemus, R. ; Hoffman, D. ; Locay, H. ; McIvor, M. ; Navarro, J. ; Pellegrini, E. ; Ramirez, G. ; Rowe, D. ; Serrano, G. ; Vacker, M. ; Weiss, R. ; Zeig, S. ; Bazemore, J. ; Frederickson, E. ; Himot, E. ; Martinez, C. ; Murphy, S. ; Nass, K. ; Obialo, C. ; Vainer, S. ; Bilinsky, R. ; Ghossein, C. ; Kamran, M. ; Leehey, D. J. ; Sparrow, R. ; Karp, Sharon ; Taber, Tim ; Kaskas, M. ; Zabaneh, R. ; Hood, S. ; Kershaw, G. ; Lazowski, P. ; Shih, D. ; Slater, J. ; Al-Talib, K. K. ; Fink, J. ; Turer, P. ; Wassem, M. ; Al-Saghir, F. ; Rao, V. ; Awad, A. ; Domoto, D. ; Mellas, J. ; Brandspigel, K. ; Spry, L. ; Eidelson, B. ; Feldman, J. ; Haratz, A. ; Huq, M. ; Lehrner, L. ; Leisrowitz, M. ; Shete, L. ; Henriquez, M. ; Hoy, C. ; Mailloux, L. ; Miller, I. J. ; Parnes, E. ; Scott, D. ; Wagner, J. ; Cohen, L. H. ; Dennis, V. W. ; Kant, K. S. ; Malhotra, D. K. ; von Hartitzsch, B. ; Kennefick, T. M. ; Benz, R. L. ; Clark, E. ; Filippone, E. ; Foti, F. ; Kurtzer, Y. B. ; Levenson, D. ; Raza, H. ; Rodenberger, C. ; Rudnick, M. ; Testa, M. A. / Extended epoetin alfa dosing as maintenance treatment for the anemia of chronic kidney disease : The PROMPT study. In: Clinical Nephrology. 2005 ; Vol. 64, No. 2. pp. 113-123.
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title = "Extended epoetin alfa dosing as maintenance treatment for the anemia of chronic kidney disease: The PROMPT study",
abstract = "Aim: To determine whether extended epoetin alfa dosing schedules of up to once every four weeks are as effective as weekly dosing in maintaining hemoglobin (Hb) levels in patients with anemia of chronic kidney disease (CKD). Methods: This randomized, open-label trial enrolled patients with anemia of CKD not on dialysis. Patients were required to have a stable Hb level (≥ 11.0 g/dl) and to have been previously receiving epoetin alfa for two or more months. Patients were randomized to one of four subcutaneously administered epoetin alfa dosing regimens: 10,000 units (U) once weekly (QW), 20,000 U every two weeks (Q2W), 30,000 U every three weeks (Q3W) or 40,000 U every four weeks (Q4W). Dose reductions, but not escalations, were permitted. Patients received treatment for a total of 16 weeks. The primary endpoint for the trial was the mean final Hb measurements of the QW, Q2W, Q3W, and Q4W groups. The primary efficacy analyses were non-inferiority assessments of the mean final Hb measurements of the Q2W, Q3W, and Q4W groups, compared with the QW group. The primary efficacy analyses were performed using a modified intent-to-treat (MITT) population, defined as all patients meeting all inclusion/exclusion criteria (or, if not satisfying all criteria, were granted an exemption at study entry), and who were randomized and received at least one dose of study medication. A per-protocol population, based on all patients who met the MITT criteria and completed the entire study, was used to evaluate the robustness of the MITT results. Quality of life was assessed for all dosing groups throughout the study. Safety was based on all patients randomized who received at least one dose of study medication. Results: A total of 519 patients were enrolled; 445 were included in the MITT population. The four treatment groups were comparable with respect to baseline characteristics. The primary etiologies of CKD were diabetes (45.7{\%}) and hypertension (29.9{\%}). The mean baseline Hb, serum creatinine and glomerular filtration rate for all patients were 11.9 ± 0.8 g/dl, 3.1 mg/dl, and 21.1 ml/min/1.73 m2, respectively. The mean baseline transferrin saturation was 25.2{\%} and the mean ferritin was 201.9 ng/ml for all patients. All groups had a mean final Hb of > 11.0 g/dl. The mean final Hb levels of the Q2W and Q4W groups were statistically non-inferior to the QW group. The results of the per-protocol analysis were consistent with the MITT results. In addition, 93.5{\%}, 89.5{\%}, 77.2{\%}, and 76.0{\%} of patients maintained a mean Hb ≥ 11.0 g/dl throughout the course of the study in the QW, Q2W, Q3W, and Q4W groups, respectively. Quality of life was maintained or improved from baseline to final within each dosing group. There were no significant differences in the mean final quality of life scores between the QW group and the Q2W, Q3W, and Q4W groups. Among the 513 patients evaluated for safety, epoetin alfa was well tolerated with no differences in adverse events between groups. The incidence of thrombotic adverse events was low (2.5{\%} of patients), as was mortality (1.4{\%} of patients). Conclusions: Approximately 90{\%} of patients dosed once every two weeks and over 75{\%} of patients dosed once every three or four weeks maintained mean Hb levels ≥ 11.0 g/dl, consistent with the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. This study suggests that extended epoetin alfa dosing schedules are effective and safe for maintaining Hb, and may offer the possibility of increased flexibility and convenience for the majority of patients with the anemia of CKD.",
keywords = "Anemia, Chronic kidney disease, Epoetin alfa, Hemoglobin",
author = "Robert Provenzano and S. Bhaduri and Singh, {A. K.} and M. Abrante and D. Chang and Lien, {Y. H.} and J. Chandrashekar and M. Dana and S. Friedman and K. Kleinman and V. Kondle and Lafayette, {R. A.} and H. Madkour and D. Makoff and Mehta, {R. L.} and D. Ricker and M. Samson and M. Shapiro and M. Spira and C. Sun and K. Tucker and M. Esson and Caanthan, {K. D.} and J. Cohen and R. Geronemus and D. Hoffman and H. Locay and M. McIvor and J. Navarro and E. Pellegrini and G. Ramirez and D. Rowe and G. Serrano and M. Vacker and R. Weiss and S. Zeig and J. Bazemore and E. Frederickson and E. Himot and C. Martinez and S. Murphy and K. Nass and C. Obialo and S. Vainer and R. Bilinsky and C. Ghossein and M. Kamran and Leehey, {D. J.} and R. Sparrow and Sharon Karp and Tim Taber and M. Kaskas and R. Zabaneh and S. Hood and G. Kershaw and P. Lazowski and D. Shih and J. Slater and Al-Talib, {K. K.} and J. Fink and P. Turer and M. Wassem and F. Al-Saghir and V. Rao and A. Awad and D. Domoto and J. Mellas and K. Brandspigel and L. Spry and B. Eidelson and J. Feldman and A. Haratz and M. Huq and L. Lehrner and M. Leisrowitz and L. Shete and M. Henriquez and C. Hoy and L. Mailloux and Miller, {I. J.} and E. Parnes and D. Scott and J. Wagner and Cohen, {L. H.} and Dennis, {V. W.} and Kant, {K. S.} and Malhotra, {D. K.} and {von Hartitzsch}, B. and Kennefick, {T. M.} and Benz, {R. L.} and E. Clark and E. Filippone and F. Foti and Kurtzer, {Y. B.} and D. Levenson and H. Raza and C. Rodenberger and M. Rudnick and Testa, {M. A.}",
year = "2005",
month = "8",
language = "English (US)",
volume = "64",
pages = "113--123",
journal = "Clinical Nephrology",
issn = "0301-0430",
publisher = "Dustri-Verlag Dr. Karl Feistle",
number = "2",

}

TY - JOUR

T1 - Extended epoetin alfa dosing as maintenance treatment for the anemia of chronic kidney disease

T2 - The PROMPT study

AU - Provenzano, Robert

AU - Bhaduri, S.

AU - Singh, A. K.

AU - Abrante, M.

AU - Chang, D.

AU - Lien, Y. H.

AU - Chandrashekar, J.

AU - Dana, M.

AU - Friedman, S.

AU - Kleinman, K.

AU - Kondle, V.

AU - Lafayette, R. A.

AU - Madkour, H.

AU - Makoff, D.

AU - Mehta, R. L.

AU - Ricker, D.

AU - Samson, M.

AU - Shapiro, M.

AU - Spira, M.

AU - Sun, C.

AU - Tucker, K.

AU - Esson, M.

AU - Caanthan, K. D.

AU - Cohen, J.

AU - Geronemus, R.

AU - Hoffman, D.

AU - Locay, H.

AU - McIvor, M.

AU - Navarro, J.

AU - Pellegrini, E.

AU - Ramirez, G.

AU - Rowe, D.

AU - Serrano, G.

AU - Vacker, M.

AU - Weiss, R.

AU - Zeig, S.

AU - Bazemore, J.

AU - Frederickson, E.

AU - Himot, E.

AU - Martinez, C.

AU - Murphy, S.

AU - Nass, K.

AU - Obialo, C.

AU - Vainer, S.

AU - Bilinsky, R.

AU - Ghossein, C.

AU - Kamran, M.

AU - Leehey, D. J.

AU - Sparrow, R.

AU - Karp, Sharon

AU - Taber, Tim

AU - Kaskas, M.

AU - Zabaneh, R.

AU - Hood, S.

AU - Kershaw, G.

AU - Lazowski, P.

AU - Shih, D.

AU - Slater, J.

AU - Al-Talib, K. K.

AU - Fink, J.

AU - Turer, P.

AU - Wassem, M.

AU - Al-Saghir, F.

AU - Rao, V.

AU - Awad, A.

AU - Domoto, D.

AU - Mellas, J.

AU - Brandspigel, K.

AU - Spry, L.

AU - Eidelson, B.

AU - Feldman, J.

AU - Haratz, A.

AU - Huq, M.

AU - Lehrner, L.

AU - Leisrowitz, M.

AU - Shete, L.

AU - Henriquez, M.

AU - Hoy, C.

AU - Mailloux, L.

AU - Miller, I. J.

AU - Parnes, E.

AU - Scott, D.

AU - Wagner, J.

AU - Cohen, L. H.

AU - Dennis, V. W.

AU - Kant, K. S.

AU - Malhotra, D. K.

AU - von Hartitzsch, B.

AU - Kennefick, T. M.

AU - Benz, R. L.

AU - Clark, E.

AU - Filippone, E.

AU - Foti, F.

AU - Kurtzer, Y. B.

AU - Levenson, D.

AU - Raza, H.

AU - Rodenberger, C.

AU - Rudnick, M.

AU - Testa, M. A.

PY - 2005/8

Y1 - 2005/8

N2 - Aim: To determine whether extended epoetin alfa dosing schedules of up to once every four weeks are as effective as weekly dosing in maintaining hemoglobin (Hb) levels in patients with anemia of chronic kidney disease (CKD). Methods: This randomized, open-label trial enrolled patients with anemia of CKD not on dialysis. Patients were required to have a stable Hb level (≥ 11.0 g/dl) and to have been previously receiving epoetin alfa for two or more months. Patients were randomized to one of four subcutaneously administered epoetin alfa dosing regimens: 10,000 units (U) once weekly (QW), 20,000 U every two weeks (Q2W), 30,000 U every three weeks (Q3W) or 40,000 U every four weeks (Q4W). Dose reductions, but not escalations, were permitted. Patients received treatment for a total of 16 weeks. The primary endpoint for the trial was the mean final Hb measurements of the QW, Q2W, Q3W, and Q4W groups. The primary efficacy analyses were non-inferiority assessments of the mean final Hb measurements of the Q2W, Q3W, and Q4W groups, compared with the QW group. The primary efficacy analyses were performed using a modified intent-to-treat (MITT) population, defined as all patients meeting all inclusion/exclusion criteria (or, if not satisfying all criteria, were granted an exemption at study entry), and who were randomized and received at least one dose of study medication. A per-protocol population, based on all patients who met the MITT criteria and completed the entire study, was used to evaluate the robustness of the MITT results. Quality of life was assessed for all dosing groups throughout the study. Safety was based on all patients randomized who received at least one dose of study medication. Results: A total of 519 patients were enrolled; 445 were included in the MITT population. The four treatment groups were comparable with respect to baseline characteristics. The primary etiologies of CKD were diabetes (45.7%) and hypertension (29.9%). The mean baseline Hb, serum creatinine and glomerular filtration rate for all patients were 11.9 ± 0.8 g/dl, 3.1 mg/dl, and 21.1 ml/min/1.73 m2, respectively. The mean baseline transferrin saturation was 25.2% and the mean ferritin was 201.9 ng/ml for all patients. All groups had a mean final Hb of > 11.0 g/dl. The mean final Hb levels of the Q2W and Q4W groups were statistically non-inferior to the QW group. The results of the per-protocol analysis were consistent with the MITT results. In addition, 93.5%, 89.5%, 77.2%, and 76.0% of patients maintained a mean Hb ≥ 11.0 g/dl throughout the course of the study in the QW, Q2W, Q3W, and Q4W groups, respectively. Quality of life was maintained or improved from baseline to final within each dosing group. There were no significant differences in the mean final quality of life scores between the QW group and the Q2W, Q3W, and Q4W groups. Among the 513 patients evaluated for safety, epoetin alfa was well tolerated with no differences in adverse events between groups. The incidence of thrombotic adverse events was low (2.5% of patients), as was mortality (1.4% of patients). Conclusions: Approximately 90% of patients dosed once every two weeks and over 75% of patients dosed once every three or four weeks maintained mean Hb levels ≥ 11.0 g/dl, consistent with the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. This study suggests that extended epoetin alfa dosing schedules are effective and safe for maintaining Hb, and may offer the possibility of increased flexibility and convenience for the majority of patients with the anemia of CKD.

AB - Aim: To determine whether extended epoetin alfa dosing schedules of up to once every four weeks are as effective as weekly dosing in maintaining hemoglobin (Hb) levels in patients with anemia of chronic kidney disease (CKD). Methods: This randomized, open-label trial enrolled patients with anemia of CKD not on dialysis. Patients were required to have a stable Hb level (≥ 11.0 g/dl) and to have been previously receiving epoetin alfa for two or more months. Patients were randomized to one of four subcutaneously administered epoetin alfa dosing regimens: 10,000 units (U) once weekly (QW), 20,000 U every two weeks (Q2W), 30,000 U every three weeks (Q3W) or 40,000 U every four weeks (Q4W). Dose reductions, but not escalations, were permitted. Patients received treatment for a total of 16 weeks. The primary endpoint for the trial was the mean final Hb measurements of the QW, Q2W, Q3W, and Q4W groups. The primary efficacy analyses were non-inferiority assessments of the mean final Hb measurements of the Q2W, Q3W, and Q4W groups, compared with the QW group. The primary efficacy analyses were performed using a modified intent-to-treat (MITT) population, defined as all patients meeting all inclusion/exclusion criteria (or, if not satisfying all criteria, were granted an exemption at study entry), and who were randomized and received at least one dose of study medication. A per-protocol population, based on all patients who met the MITT criteria and completed the entire study, was used to evaluate the robustness of the MITT results. Quality of life was assessed for all dosing groups throughout the study. Safety was based on all patients randomized who received at least one dose of study medication. Results: A total of 519 patients were enrolled; 445 were included in the MITT population. The four treatment groups were comparable with respect to baseline characteristics. The primary etiologies of CKD were diabetes (45.7%) and hypertension (29.9%). The mean baseline Hb, serum creatinine and glomerular filtration rate for all patients were 11.9 ± 0.8 g/dl, 3.1 mg/dl, and 21.1 ml/min/1.73 m2, respectively. The mean baseline transferrin saturation was 25.2% and the mean ferritin was 201.9 ng/ml for all patients. All groups had a mean final Hb of > 11.0 g/dl. The mean final Hb levels of the Q2W and Q4W groups were statistically non-inferior to the QW group. The results of the per-protocol analysis were consistent with the MITT results. In addition, 93.5%, 89.5%, 77.2%, and 76.0% of patients maintained a mean Hb ≥ 11.0 g/dl throughout the course of the study in the QW, Q2W, Q3W, and Q4W groups, respectively. Quality of life was maintained or improved from baseline to final within each dosing group. There were no significant differences in the mean final quality of life scores between the QW group and the Q2W, Q3W, and Q4W groups. Among the 513 patients evaluated for safety, epoetin alfa was well tolerated with no differences in adverse events between groups. The incidence of thrombotic adverse events was low (2.5% of patients), as was mortality (1.4% of patients). Conclusions: Approximately 90% of patients dosed once every two weeks and over 75% of patients dosed once every three or four weeks maintained mean Hb levels ≥ 11.0 g/dl, consistent with the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. This study suggests that extended epoetin alfa dosing schedules are effective and safe for maintaining Hb, and may offer the possibility of increased flexibility and convenience for the majority of patients with the anemia of CKD.

KW - Anemia

KW - Chronic kidney disease

KW - Epoetin alfa

KW - Hemoglobin

UR - http://www.scopus.com/inward/record.url?scp=23144460027&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23144460027&partnerID=8YFLogxK

M3 - Article

C2 - 16114787

AN - SCOPUS:23144460027

VL - 64

SP - 113

EP - 123

JO - Clinical Nephrology

JF - Clinical Nephrology

SN - 0301-0430

IS - 2

ER -