Chronic Kidney Disease
Conditions
Keywords
phosphorus, secondary hyperparathyroidism, vascular calcification
Brief summary
The purpose of this study is to determine the ability of 3 commercially available phosphorus binders (calcium acetate, sevelamer carbonate, and lanthanum carbonate) to achieve and maintain a phosphorus level in the normal range in patients with chronic kidney disease.
Detailed description
It is the specific aim of this pilot study to assess the feasibility of achieving and maintaining a serum P less than or equal to 3.5 mg/dL (1.13 mmol/L) in patients with eGFR \>20 and \<45 mL/min with any of the 3 commercially available P lowering agents (calcium acetate, sevelamer carbonate, or lanthanum carbonate). Results of this study will clarify the degree of separation in serum P that can be achieved with the use of P lowering agents and the current standard of care (P binder initiation when P \> 5.5 mg/dL or 1.78 mmol/L). Furthermore, this knowledge, combined with analyses of the secondary aims and outcomes of interest, will serve to facilitate the design of a properly powered, randomized, placebo controlled clinical outcomes trial that will firmly establish the necessity of achieving a specific target P in patients with CKD. The secondary aims of this pilot study are to provide insight into the optimal detection of progression of abnormalities in mineral metabolism and their relationship to vascular disease in CKD. The tertiary aim is to evaluate long term outcomes related to phosphorus normalization with respect to renal replacement therapy or death.
Interventions
Sponsors
Shire
Fresenius Medical Care North America
Genzyme, a Sanofi Company
Novartis Pharmaceuticals
DaVita, Inc.
Denver Nephrologists, P.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women \> 18 years of age; * Has signed and dated the most recent informed consent form approved by an IRB; * Will, in the opinion of the PI, be compliant with prescribed phosphate binder therapy; * Must be able to communicate with the investigator, and be able to understand and comply with the requirements of the study; * Has a life expectancy \>12 months; * An eGFR rate (estimated by the MDRD equation) ≥ 20 and ≤ 45 mL/min/1.73m2 obtained by screening laboratory values and in the opinion of the investigator felt to have CKD without evidence of recent acute kidney injury or unexpected decline in renal function; * A screening serum phosphorus value \> 3.5 mg/dL and ≤ 6.0 mg/dL; * Must consume a minimum of 2 meals per day and be willing to avoid intentional changes in diet; * Women of child bearing potential must be practicing an acceptable form of birth control.
Exclusion criteria
* Receiving or has received an investigational drug (or is currently using an investigational device) within 30 days prior to baseline; * Subject is pregnant, is breast feeding or is of child bearing potential and not using acceptable birth control measures; * Has had a previous renal transplant; * Has a chronic reliance on enemas or laxatives; * Has a known sensitivity or previous intolerance to any of the products to be administered during the study; * Clinical evidence of active malignancy and/or receiving systemic chemotherapy/radiotherapy with the exception of basal cell or squamous carcinoma of the skin; * Currently has an active infection or is being treated with antibiotics (within 14 days prior to baseline); * Has been hospitalized within 30 days prior to baseline (with the exception of hospitalizations due to vascular access procedures); * Any surgical or medical condition which might significantly alter the function of phosphorus binders or which may jeopardize the subject in case of participation in the study. The investigator should be guided by evidence of any of the following: Severe gastrointestinal motility disorder,Bowel obstruction,Dysphagia or other disorders of swallowing, Acute peptic ulcer, Ulcerative colitis or Crohn's disease, History of major gastrointestinal tract surgery, Severe malabsorption; * Currently taking any of the following within 14 days prior to baseline; Calcitriol or its analogs, Cinacalcet hydrochloride, Medications prescribed for the purpose of phosphorus binding; * Screening serum intact PTH \>500 pg/mL; * Screening corrected calcium \< 8.0 mg/dL or \> 10.4 mg/dL; * Uncontrolled hyperlipidemia in the opinion of the PI; * Initiation of chronic maintenance hemodialysis planned within 12 months; * Relocation to another area planned within 12 months; * Has a known history of immunodeficiency diseases, including a positive HIV test result; * Active drug or alcohol dependence or abuse (excluding tobacco use) within the 12 months prior to dosing or evidence of such abuse; * Evidence of active liver disease with AST or ALT levels greater than 3X the upper limit of normal; * Has had a major cardiovascular event within 180 days of screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Phosphorus | months 3-9 | mean serum phosphorus from months 3-9 |
Countries
United States
Participant flow
Recruitment details
Single center private practice single specialty clinic, Enrollment Feb 2009 thru September 2010
Pre-assignment details
Consecutive CKD patients with eGFR 20- 45 ml/min with serum Phosphorus \>3.5 \< 6.0. Stratified by diabetic status. 3 subjects were enrolled but did not receive study medication due to withdrawal prior to starting medication.
Participants by arm
| Arm | Count |
|---|---|
| Calcium Acetate phosphate binder : starting dose 667mg;titrations to 2668mg QAC | 30 |
| Sevelamer Carbonate phosphate binder : starting dose 800mg; titrations to 3200mg QAC | 30 |
| Lanthanum Carbonate phosphate binder : starting dose 500mg; titrations to 1500mg QAC | 28 |
| Placebo | 57 |
| Total | 145 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | administrative decision | 5 | 1 | 3 | 4 |
| Overall Study | Adverse Event | 2 | 1 | 1 | 5 |
| Overall Study | Protocol Violation | 1 | 2 | 4 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 2 | 2 |
Baseline characteristics
| Characteristic | Calcium Acetate | Sevelamer Carbonate | Lanthanum Carbonate | Placebo | Total |
|---|---|---|---|---|---|
| Age Continuous | 68 years STANDARD_DEVIATION 12 | 66 years STANDARD_DEVIATION 12 | 70 years STANDARD_DEVIATION 10 | 65 years STANDARD_DEVIATION 12 | 67 years STANDARD_DEVIATION 12 |
| Region of Enrollment United States | 30 participants | 30 participants | 28 participants | 57 participants | 145 participants |
| Sex: Female, Male Female | 14 Participants | 15 Participants | 13 Participants | 29 Participants | 71 Participants |
| Sex: Female, Male Male | 16 Participants | 15 Participants | 15 Participants | 28 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 43 / 57 | 21 / 28 | 25 / 30 | 26 / 30 |
| serious Total, serious adverse events | 8 / 57 | 6 / 28 | 8 / 30 | 4 / 30 |
Outcome results
Primary
Serum Phosphorus
mean serum phosphorus from months 3-9
Time frame: months 3-9
Population: ITT analysis was ALL active patients combined versus all placebo patients combined
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Active Treated Patients | Serum Phosphorus | 3.9 mg/dL | Standard Deviation 0.4 |
| All Placebo Treated Patients | Serum Phosphorus | 4.2 mg/dL | Standard Deviation 0.4 |