The Effect of Phosphate Lowering Using Sucroferric Oxyhydroxide (PA21) on Calcification Propensity of Serum

Phase 2

Completed

• Conditions: Endstage Renal Disease
• Interventions: Drug: high-dose sucroferric oxyhydroxide; Drug: low-dose sucroferric oxyhydroxide

• Registration Number: NCT03010072
• Lead Sponsor: Prim. Priv. Doz. Dr. Daniel Cejka

Brief Summary

This is a single-center, prospective, open-label, controlled, randomized, cross-over study in 34 prevalent end-stage renal disease patients on chronic hemodialysis treatment with hyperphosphatemia.

Detailed Description

Patients will be randomized in a 1:1 ratio to either receive low-dose (250mg/d) PA-21 followed by high-dose (2000mg/d) PA-21 (sequence A-B) or to receive high-dose PA21 followed by low-dose PA21 (sequence B-A) with washout-phases in between. An open label design with a sub-therapeutic dose of PA21 as control treatment was chosen because creating a convincing placebo for PA21 is not feasible.

The study will start with two study visits on the 2nd and 3rd dialysis session of the week , where dialysis patients are still treated with standard of care to establish baseline values (duration: 0.5 weeks). Next will be an initial run-in wash-out phase, where all phosphate binders taken by the patient as standard of care treatment will be discontinued and no phosphate binders will be introduced. Consequently, there will be a PA21 treatment (high dose/low dose) phase, followed by a wash-out phase, followed by another PA21 treatment (high dose/low dose) phase, followed by a final wash-out phase. Each study phase, including wash-out phases as well as low-dose and high-dose treatment phases will be 14 days of duration. Patients will be followed up to 10.5 weeks after randomization until the last study visit of the final wash-out phase.

Study Timeline

• Study First Submitted: 2016-12-22
• Study First Submitted QC: 2017-01-03
• Study First Posted: 2017-01-04
• Study Start: 2017-06-09
• Primary Completion: 2018-12-31
• Study Completion: 2019-05-10
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-19
• Last Update Posted: 2019-07-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Prevalent patients (≥ 3 months on dialysis) treated with thrice weekly hemodialysis (HD) or hemodiafiltration (HDF)
• Hyperphosphatemia (serum phosphate > upper limit of normal within the last 3 months) or current phosphate binder use
• No use or constant dose of vitamin D and/or calcimimetics for ≥2 weeks

Exclusion Criteria

• Allergy to sucroferric oxyhydroxide (PA21), to other ingredients of Velphoro or to any iron-medication
• Current or history of calciphylaxis (calcific uremic arteriolopathy - CUA)
• parathormone >800 pg/ml
• Parathyreoidektomie planned or expected
• Significant GI or hepatic disorders
• Hypercalcemia (total serum calcium >2.6 mmol/l) at screening
• Antacids containing aluminum, calcium, magnesium or bicarbonate
• Oral iron treatments/supplements
• Pregnant and nursing (lactating) women

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
high-dose sucroferric oxyhydroxide	high-dose sucroferric oxyhydroxide	Uniform dose 2000 mg of sucroferric oxyhydroxide (PA21) per day (4x 500mg tablets/day) for 14 days
low-dose sucroferric oxyhydroxide	low-dose sucroferric oxyhydroxide	Low dose 250 mg sucroferric oxyhydroxide (PA21) per day (1x 250mg tablets/day) for 14 days.

Primary Outcome Measures

Name	Time	Method
Propensity of serum for calcification - H1	10.5 weeks	The primary outcome is change in the mean T50- Test values between different study phases (wash-out/treatment/control).

Secondary Outcome Measures

Name	Time	Method
Change in Serum Phosphate	10.5 weeks	The secondary outcome is the Change of mean Serum Phosphate Levels between different study visits

Trial Locations

Locations (1)

Ordensklinikum Linz GmbH Elisabethinen; 🇦🇹 Linz, Upper Austria, Austria