Clinical and Experimental Nephrology

, Volume 9, Issue 3, pp 219–227 | Cite as

Study design and methods for a clinical trial of an oral carbonaceous adsorbent used to prevent the progression of chronic kidney disease (CAP-KD)

  • Satoshi Morita
  • Shunichi Fukuhara
  • Tadao Akizawa
  • Yasushi Asano
  • Kiyoshi Kurokawa
ORIGINAL ARTICLE

Abstract

Background

The number of patients with chronic kidney disease (CKD) in Japan is currently rising. Therefore, measures to control the progression of CKD from a predialysis condition to endstage renal failure are urgently required. We are conducting a clinical trial to investigate the efficacy of an oral carbonaceous adsorbent (Kremezin) in patients at the predialysis stage of progressive chronic kidney disease (the Carbonaceous oral Adsorbent's effectiveness on Progression of chronic Kidney Disease [CAP-KD] trial).

Methods

A multidisciplinary treatment regimen, consisting of antihypertensive therapy (using an angiotensin-converting-enzyme inhibitor and/or an angiotensin II receptor blocker) and a low-protein diet is conventionally used to treat patients with kidney disease. To assess the efficacy of Kremezin in preventing the progression of CKD, we compare two groups of patients, receiving either conventional treatment alone or such treatment paired with Kremezin. The CAP-KD trial is a prospective, multicenter, randomized, open-label, two-arm, parallel-group comparison clinical trial and will be conducted as a researcher-directed study. The primary endpoint of this study is the time to the first event of a composite endpoint, comprising the following: (1) a doubling of serum creatinine (sCr); (2) an increase in sCr level to 6.0 mg/dl or more; (3) endstage renal disease (defined as that requiring dialysis or renal transplantation); and (4) death. Secondary endpoints are as follows: (1) variation in urinary protein; (2) changes in creatinine clearance rate; (3) changes in health-related quality of life; and (4) adverse events. The total number of patients (putative) in this trial will be 450, with 225 patients in each group. Enrollment will take place over 2 years, with a 1-year follow-up period.

Results

As this is an ongoing trial, results are not yet available.

Conclusions

We believe that the CAP-KD trial is a well-designed study that will provide internationally relevant evidence concerning the outcomes of treatment in Japanese patients with CKD.

Key words

Chronic kidney disease Oral carbonaceous adsorbent Randomized clinical trial Composite endpoint 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Japanese Society for Dialysis Therapy Statistics Investigation Committee2004An overview of regular dialysis treatment in Japan (as of 31 Dec 2001)Ther Apher Dial8132Google Scholar
  2. 2.
    Klahr, S, Levey, AS, Beck, GJ, Caggiula, AW, Hunsicker, L, Kusek, JW,  et al. 1994The effect of dietary protein restriction and blood pressure control on the progression of chronic renal disease: Modification of Diet in Renal Disease Study GroupN Engl J Med33087784CrossRefPubMedGoogle Scholar
  3. 3.
    Modification of Diet in Renal Disease Study Group1996Effect of dietary protein restriction on the progression of moderate renal disease in the Modification of Diet in Renal Disease StudyJ Am Soc Nephrol7261626Google Scholar
  4. 4.
    Heart Outcomes Prevention Evaluation (HOPE) Study Investigators2000Effects of ramipril on cardiovascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudyLancet3552539Google Scholar
  5. 5.
    Ravid, M, Savin, H, Jutrin, I, Bental, T, Katz, B, Lishner, M,  et al. 1993Long-term stabilizing effect of angiotensin converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patientsAnn Intern Med11857781PubMedGoogle Scholar
  6. 6.
    Maschio, G, Alberti, D, Janin, G, Locatelli, F, Mann, JF, Motolese, M,  et al. 1996Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency: The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Research GroupN Engl J Med33493945CrossRefPubMedGoogle Scholar
  7. 7.
    The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nephrologia)1997Randomized placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathyLancet349185763Google Scholar
  8. 8.
    Brenner, BM Cooper, ME de Zeeuw, D Keane, WF Mitch, WE Parving, HH for the RENAAL Study Investigators et al. 2001Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathyN Engl J Med3458619PubMedGoogle Scholar
  9. 9.
    Lewis, EJ Hunsicker, LG Clarke, WR Berl, T Pohl, MA Lewis, JB for the Collaborative Study Group et al. 2001Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type-2 diabetesN Engl J Med34585160CrossRefPubMedGoogle Scholar
  10. 10.
    Parving, HH Lehnert, H Brochner-Mortensen, J Gomis, R Andersen, S Arner, P for the Irbesartan in Patients with Type-2 Diabetes and Microalbuminuria Study Group2001The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetesN Engl J Med3458708CrossRefPubMedGoogle Scholar
  11. 11.
    Nakao, N, Yoshimura, A, Morita, H, Takada, M, Kayano, T, Ideura, T 2003Combination treatment of angiotensin-II receptor blocker and angiotensin-converting enzyme-inhibitor in non-diabetic renal disease (COOPERATE): a randomized controlled trialLancet36111724CrossRefPubMedGoogle Scholar
  12. 12.
    Akizawa, T, Koide, K, Koshikawa, S 1998Effects of Kremezin on patients with chronic renal failure: results of a nationwide clinical studyKidney and Dialysis4537388(in Japanese)Google Scholar
  13. 13.
    Koshikawa, S,  et al. 1987The effect of AST-120 on the course of chronic renal insufficiencyKidney and Dialysis2237381(in Japanese)Google Scholar
  14. 14.
    Koide, K, Koshikawa, S, Yamane, K, Hidaka, S, Sekino, H, Saito, M,  et al. 1987Clinical evaluation of AST-120 on suppression of progression of chronic renal failure: multi-center, double-blind study in comparison with placeboClinical Evaluation1552764(in Japanese)Google Scholar
  15. 15.
    Pocock, SJ, Simon, R 1975Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trialBiometrics11031Google Scholar
  16. 16.
    Horio, M, Orita, Y, Manabe, S, Sakata, M, Fukunaga, M 1997Formula and nomogram for predicting creatinine clearance from serum creatinine concentrationClin Exp Nephrol11104Google Scholar
  17. 17.
    Ware, J, Kosinski, M, Dewey, J 2000How to score version 2 of SF-36R health surveyQualityMetricLincoln, RIGoogle Scholar
  18. 18.
    Mark, SD, Robins, JM 1993A method for the analysis of randomized trials with complianceinformation: an application to the Multiple Risk Factor Intervention Trial. Controlled Clin Trials147997Google Scholar

Copyright information

© Japanese Society of Nephrology 2005

Authors and Affiliations

  • Satoshi Morita
    • 1
  • Shunichi Fukuhara
    • 1
  • Tadao Akizawa
    • 2
  • Yasushi Asano
    • 3
  • Kiyoshi Kurokawa
    • 4
  1. 1.Department of Epidemiology and Health Care ResearchKyoto University Graduate School of MedicineKyotoJapan
  2. 2.Center of Blood Purification TherapyWakayama Medical SchoolWakayamaJapan
  3. 3.Department of Internal MedicineJichi Medical School and Sashima Red Cross HospitalTochigiJapan
  4. 4.The Research Center for Advanced Science and TechnologyUniversity of TokyoTokyoJapan

Personalised recommendations