Correcting Anemia and Native Vitamin D Supplementation in Kidney Transplant Recipients

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

161 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-04-30

Study Completion Date

2018-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The purpose of this study is to evaluate the effect of anemia correction and vitamin D supplementation in kidney transplant recipients.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Vitamin D Supplementation in Glomerular Disease

NCT01835639

Glomerular Disease

COMPLETED NA

Vitamin D as a Modifier of Serum Hepcidin in Children With Chronic Kidney Disease

NCT01532349

Anemia of Chronic Kidney Disease

COMPLETED PHASE2

Effect of Vitamin D Supplementation on Erythropoietin Dosage in Hemodialysis Patients Who Have Vitamin D Deficiency

NCT00915317

Vitamin D Deficiency Anemia

WITHDRAWN

Efficacy of Usual Vitamin D Supplementation and Its Impact on Children and Adolescents Calciuria.

NCT02238418

Chronic Kidney Disease Renal Transplantation Nephrotic Syndrome

COMPLETED PHASE4

Supplementation With Cholecalciferol in Dialysis Patients

NCT01974245

Chronic Kidney Disease

COMPLETED PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Sample size estimation:

The previous trial (the CAPRIT study) showed that 2.0 g/dL increase of hemoglobin (Hb) reduced 69% of 2-year decline in estimated glomerular filtration rate (eGFR) (Choukroun G, et al. J Am Soc Nephrol, 2012). Given that the annual eGFR decline in our patients with Hb level \<10.5 g/dL was 1.66 (SD, 2.47) mL/min per 1.73 m2, the investigators hypothesized that the 2-year eGFR decline in the conservative anemia management group and the aggressive anemia correction group should be 3.32 (SD, 4.94) and 1.03 (SD, 4.94) mL/min per 1.73 m2, respectively. In order to compare the actual efficacy of the intervention with the assumptions above and to evaluate the need for an early termination of the trial, the investigators will perform one interim analysis using a Pocock type α-spending function when a total of 50-60% of the target sample size completed this study or dropped out. Assuming 20% of dropout or lost-to-follow, the planned sample size of 272 patients would yield a power of 90% for group comparison by using t-test with a type I error of 5%.

Regarding cholecalciferol supplementation, 1,000 IU/day would increase serum 25-hydroxyvitamin D level by 11.8 ng/mL in patients with BMI \<30, as suggested by the previous trial (Gallagher JC, et al. Ann Intern Med, 2012). The investigators found in our prospective cohort study that the 98.2% of Japanese kidney transplant recipients had BMI \<30, and that 10 ng/mL increase in 25-hydroxyvitamin D level was significantly associated with 0.75 mL/min/1.73 m2 less decrease in annual eGFR change independent of potential confounders (in submission). As with the anemia intervention arms above, the investigators will perform one interim analysis using a Pocock type α-spending function when a total of 50-60% of the target sample size completed this study or dropped out in order to compare the actual efficacy of the intervention with the assumptions above and to evaluate the need for an early termination of the trial. Therefore, the investigators expect 1.77 mL/min per 1.73 m2 in eGFR would be preserved by 1,000 IU/day of cholecalciferol supplementation for 2 years. Based on this assumption, this study size will provide a power of 70%.

Estimating kidney function:

In primary analyses, eGFR will be calculated by using the Japanese equation as in sample size calculation (Matsuo S, et al. Am J Kidney Dis, 2009). However, this formula has not yet been validated in kidney transplant recipients. Therefore, the investigators will use the creatinine-based CKD-EPI equation with Japanese coefficient (Stevens LA, et al. Nephrol Dial Transplant, 2010. Horio M, et al. Am J Kidney Dis, 2010) and an available formula if validated in Japanese kidney transplant recipients at the time of analysis.

Statistical analyses:

For group comparison in a primary analysis, the investigators will use t-test or Wilcoxon rank sum test according to the distribution of eGFR change. In the further analyses, to analyze the time course of eGFR with respect to treatment assignment, changes in eGFR over time will be analyzed with a linear mixed model for repeated measures with both fixed and random intercept and slope. The multivariate model will contain time-varying eGFR as dependent variable and treatment group as well as the number of measurements (time) as independent variables. The study hypothesis will be tested by adding appropriate interaction terms between the exposures and time. For secondary endpoints, the investigators will use t-test, Wilcoxon rank sum test, or log-rank test for group comparison, and generalized linear models or Cox proportional hazards models to estimate each effect of the interventions, appropriately. The investigators will also adjust for baseline levels or past history of each outcome. Other potential confounders, such as age, sex, time since transplantation, blood pressure, urinary protein level, and diabetes, will be adjusted in sensitivity analyses.

The interaction will be checked between anemia management and cholecalciferol supplementation as well as between each intervention and baseline levels of urinary protein, eGFR, Hb, 25-hydroxyvitamin D, the use of active vitamin D compounds, and the length of time since transplantation. Additionally, stratified analyses will be conducted according to 0.2 g/g･creatinine of urinary protein and the date of transplantation (November 1999, the release date of mycophenolate mofetil in Japan). However, the study size is not large enough to statistically evaluate these interactions. The results from these analyses should be interpreted with caution and regarded as exploratory and hypothesis generating.

Missing values:

Missing values will not be imputed in primary analyses. In sensitivity analyses, the investigators will use multiple imputation method and last-observation-carried-forward method.

Note:

The interim analysis plan was added to the protocol with an increase in the sample size from 246 to 272, which has been approved by the local ethics committee on August 27, 2018.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Kidney Transplantation Anemia Vitamin D Deficiency Renal Insufficiency, Chronic

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Low Hb target without cholecalciferol

Target Hemoglobin level: ≥9.5 and \<10.5 g/dL

Group Type NO_INTERVENTION

No interventions assigned to this group

Low Hb target with cholecalciferol

Target Hemoglobin level: ≥9.5 and \<10.5 g/dL Cholecalciferol: 1,000 IU/day

Group Type ACTIVE_COMPARATOR

cholecalciferol

Intervention Type DIETARY_SUPPLEMENT

1,000 IU (1 tablet)/day, orally. Tablets are repacked into blister package.

High Hb target without cholecalciferol

Target Hemoglobin level: ≥12.5 and \<13.5 g/dL

Group Type ACTIVE_COMPARATOR

High Hb target

Intervention Type OTHER

25 to 250 μg of methoxy polyethylene glycol epoetin beta (Mircera®, Chugai pharmaceutical Co. Ltd.) will be administered subcutaneously at 2- to 6-week interval.

Dose and interval will be adjusted according to hemoglobin level and its target.

High Hb target with cholecalciferol

Target Hemoglobin level: ≥12.5 and \<13.5 g/dL Cholecalciferol: 1,000 IU/day

Group Type EXPERIMENTAL

High Hb target

Intervention Type OTHER

25 to 250 μg of methoxy polyethylene glycol epoetin beta (Mircera®, Chugai pharmaceutical Co. Ltd.) will be administered subcutaneously at 2- to 6-week interval.

Dose and interval will be adjusted according to hemoglobin level and its target.

cholecalciferol

Intervention Type DIETARY_SUPPLEMENT

1,000 IU (1 tablet)/day, orally. Tablets are repacked into blister package.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

High Hb target

25 to 250 μg of methoxy polyethylene glycol epoetin beta (Mircera®, Chugai pharmaceutical Co. Ltd.) will be administered subcutaneously at 2- to 6-week interval.

Dose and interval will be adjusted according to hemoglobin level and its target.

Intervention Type OTHER

cholecalciferol

1,000 IU (1 tablet)/day, orally. Tablets are repacked into blister package.

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Super vitamin D (Nature Made®)

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* ≥15 and \<60 ml/min per 1.73 m2 of estimated glomerular filtration rate
* Transplanted allograft kidney at least 1 year before
* \<10.5 g/dL of Hb without iron deficiency (serum ferritin level ≥50 ng/ml) or on erythropoiesis stimulating agents treatment regardless of iron status
* With written informed consent

Exclusion Criteria

* On anticancer treatment
* History of ischemic stroke or transient ischemic attack
* Corrected serum calcium ≥10.5 mg/dL
* HIV virus infection
* Anticipated refractory hypertension by using epoetin beta pegol
* In pregnancy and lactation
* Current use of native vitamin D supplement
* Patients ineligible according to the investigator's judgement

Minimum Eligible Age

20 Years

Maximum Eligible Age

79 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No