Clinical trial NCT00660530: Chewed vs. Crushed Lanthanum Carbonate in Hemodialysis Patients
Official title: An Evaluation of Chewed vs. Crushed Lanthanum Carbonate in the Efficacy of Phosphate Binding in Hemodialysis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hyperphosphatemia
Kidney Disease
Keywords: stage 5
chronic
hemodialysis
Lead sponsor: University of Illinois at Chicago
Sponsor class: OTHER
Collaborators: name: Shire
First posted: 2008-04-17
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Patients with end-stage renal disease (ESRD) commonly develop hyperphosphatemia due to the loss of excretory function of the kidney. This in turn may lead to the development of secondary hyperparathyroidism (SHPT) and renal osteodystrophy. Lanthanum carbonate, a phosphate binding agent, works by releasing lanthanum ions in the gastrointestinal tract to bind dietary phosphate and is effective in the management of hyperphosphatemia and in preventing secondary hyperparathyroidism.

Patients taking lanthanum carbonate as part of their phosphate binder therapy are counseled to chew the tablets completely before swallowing, with or immediately after meals. However, ESRD patients who are intubated or are receiving enteral tube feedings are unable to chew the lanthanum carbonate tablets. For such patients, medications are commonly crushed and administered through a gastrostomy tube (G-tube). Some patients may also prefer to crush the lanthanum carbonate tablets and mix it with food instead of chewing. To date, it is not known if crushing the lanthanum carbonate tablets prior to administration and taking it with food will be as efficacious as chewing it.

The objective of this study is to compare the efficacy of phosphate binding between chewed and crushed lanthanum carbonate in patients undergoing hemodialysis.

Detailed description: Study subjects Men and women at least 18 years of age, receiving HD for at least 3 months, with serum P concentrations 45.5 mg/dL at the end of the washout period, and on a stable dose of P binder and/or active vitamin D (if prescribed previously) for at least 1 month before the study were eligible for study participation. Patients were excluded if they did not respond to P binder therapy previously, had a known noncompliance with oral medications (e.g., failure to ﬁll a prescription or to take medications as prescribed), severe hyperparathyroidism deﬁned as intact-PTH (i-PTH) 4500 pg/mL, were taking any calcium (Ca)-, magnesium-, or aluminum-containing antacids or used an investigational agent within 30 days of study entry.

Study design This study was approved by the University of Illinois at Chicago Institutional Review Board. Informed consent was obtained from the subjects before any study procedures were initiated. One week before the administration of crushed or chewed lanthanum, the subjects were in-structed to discontinue their P-binding agents (calcium carbonate, calcium acetate, sevelamer hydrochloride, and/or lanthanum carbonate), if prescribed previously. At the end of the 1-week washout period, subjects whose serum P exceeded 5.5 mg/dL were randomized to receive, in a crossover fashion, lanthanum 1000 mg (Fosrenol, Shire US Inc., Wayne, PA, USA) 3 times daily to be chewed with meals (chewed LAN) or lanthanum 1000 mg crushed into a ﬁne powder and taken with meals 3 times daily (crushed LAN), for 4 weeks each. The lanthanum tablets were crushed into a ﬁne powder using a mortar and pestle by the investigators, individually wrapped in powder packets and dispensed to the subjects on a weekly basis. The subjects were instructed to empty the powder into a small plastic cup provided, mix with 2 tablespoonfuls of applesauce and take it with meals. After each treatment (chewed or crushed LAN), there was a 1-week washout period.

Throughout the course of the study, the subjects were asked to keep a constant dietary P intake. In addition, each subject was provided with a dietary log for recording their daily dietary intake.

Sample collection and study endpoints Blood samples were collected at the end of each washout period (baseline) and weekly (weeks 1-4) during lanthanum treatment for the determination of serum P, Ca, i-PTH, and albumin (alb) concentrations. Changes in serum P from baseline for crushed and chewed lanthanum were compared. In addition, the study subjects were asked to complete a questionnaire to assess the presence of any study-related adverse events at the end of each treatment arm.

Statistical considerations Assuming a coefﬁcient variation of 15% to 25% for serum P concentrations, a sample size of 11 to 15 was estimated to provide at least 80% power to detect a 25% difference in serum P between study treatments, using a 2-sided test and a of 0.05. Statistical analyses were performed using PASW (SPSS), version 17.0 (Chicago, IL, USA). Descriptive statistics were used to report all results. The changes in serum P, Ca, i-PTH, and alb were compared between the 2 treatment arms using paired sample t test. A P value \<0.05 was considered statistically significant.

Eligibility criteria: Inclusion Criteria:

* Male or female 18 years of age or older
* Have been on hemodialysis for at least 3 months
* Women of child-bearing potential (premenopausal and not surgically sterilized) who have a negative serum pregnancy test
* On a stable dose of phosphate binder for at least 1 month prior to the study
* On a stable dose of active vitamin D (if previously prescribed) for at least 1 month prior to the study
* Serum phosphorus concentrations \> 5.5 mg/dL (1.78 mmol/L) at the end of the washout period

Exclusion Criteria:

* Did not previously respond to phosphate binder therapy
* Known non-compliance with oral medications
* Severe hyperparathyroidism defined as intact-PTH (i-PTH) \> 500 pg/ml
* Taking any calcium-, magnesium- or aluminum-containing antacids
* Use of an investigational agent within 30 days of study entry

Primary outcomes:
measure: Serum Phosphorous Concentration
timeFrame: Week 1-4 mean
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
Study officials:
affiliation: Univsersity of Illinois at Chicago
name: Alan H Lau, Pharm.D.
role: PRINCIPAL_INVESTIGATOR
References: