Optimal Anemia Treatment in End Stage Renal Disease (ERSD) (OPTIMAL)

September 12, 2015 updated by: Azienda Ospedaliera Sant'Anna

Single-center, Open-label, Randomized Study of Anemia Management Improvement in End Stage Renal Disease (ESRD) Patients With Secondary Hyperparathyroidism

Clinical study aimed at improving anemia management in End Stage Renal Disease Patient (ESRD) on maintenance Hemodialysis with evidence of Chronic Kidney disease Mineral Bone Disorder (CKD-MBD)

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Anemia is one of the most worrisome complications of Chronic Kidney Disease (CKD). Numerous prospective studies have repeatedly documented an increase risk of morbidity and mortality associated with lower levels of hemoglobin (Hb). Hence the international guidelines on patient care suggest the use of Erythropoietin Stimulating Agents (ESA), iron, folates supplementation for anemia correction.

However, recent randomized controlled trials (RCT) have demonstrated that hemoglobin correction to normal levels increases the risk of major cardiovascular (CV) events. Though, the reasons are still unclear, the cumulative ESA dose may at least partly explain these findings suggesting limiting ESA to the minimal dose allowed to achieve the suggested Hb targets in ESRD patients.

Among other factors, CKD-MBD has been repeatedly associated with poor more severe anemia and higher dose of ESA. However, the latest Kidney Disease: Improving Global Outcomes (KDIGO) guidelines on CKD-MBD management suggest a higher reference target for intact parathyroid hormone (iPTH) (2-9 fold the upper level of the normal range) when compared to the National Kidney Foundation (NKF) guidelines published in 2003 (150-300 pg/ml).

A few observational studies suggest a linear inverse association between intact iPTH and ESA dose even for iPTH value within the iPTH target level proposed by the KDIGO working group. Similarly, a large body of evidence supports the notion that the higher the iPTH the faster the CV system deterioration in ESRD.

Aim of the study is to test whether a tighter iPTH control to achieve a iPTH level lower than 300 pg/ml vs iPTH levels between 300-540 pg/ml is associated with a ESA dose reduction and a slower CV system deterioration in ESRD patients receiving dialysis.

STUDY DESIGN Pilot, single center, open label with blinded end point (PROBE-Prospective Randomized Open Blinded End-Point) aimed at improving patient care.

Eligible patients will be randomized (1:1) to either:

(A) Control group: standard care. The iPTH target in this group is 300-540 pg/ml (B) Optimal CKD-MBD control: in this group the iPTH target is150-300 pg/ml to be achieved with a therapeutic algorithm.

TREATMENTS

All patients will be randomized (1:1) to either:

(A) Control group: standard care. The iPTH target in this group is 300-540 pg/ml.

(B) Optimal CKD-MBD control:: in this group the iPTH target is 150-300 pg/ml to be achieved with a therapeutic algorithm:

I. iPTH control: in order to achieve the iPTH target (150-300 pg/ml), all patients will receive 400 IU/day of vitamin-25-OH-D (25OHD) and a flexible dose of any active vitamin D available in Italy (calcitriol and paricalcitol-"Zemplar®") at the maximum dose of 6 mcg/week of paricalcitol("Zemplar®")of equivalent (see existing conversion table). Patients will also receive a flexible dose of cinacalcet("Mimpara®") to a maximum dose of 90 mg/day.

II. Phosphorous control: all patients need to achieve a serum phosphorous level lower than 5.5 mg/dl. All available phosphate binders are allowed [sevelamer("Renvela®"), calcium carbonate, calcium acetate("Phoslo®"), calcium acetate/magnesium carbonate ("Osvaren®"), lanthanum carbonate "Foznol®"). A rescue therapy with aluminum("Maalox®") is allowed for no more than 30 days.

III. Serum calcium control: the suggested target is less than 9.5 mg/dl. In case of serum calcium greater than 9.5 mg/dl the calcium and vitamin D dose should be lowered in order to lower the risk of vascular calcification deposition and progression

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • San Fermo della battaglia (CO), Italy, 22020
        • Recruiting
        • Azienda Ospedaliera Sant'Anna
        • Contact:
        • Principal Investigator:
          • Antonio Bellasi, MD
        • Principal Investigator:
          • Claudio Minoretti, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

INCLUSION CRITERIA.

  • Men and women
  • Age >18 years
  • Maintenance dialysis via Artero-Venous fistula
  • ESA use
  • iPTH between 300-600 pg/ml
  • Hb between 10.0-11.5
  • Kt/V greater/equal than 1.2
  • Signed informed consent prior to the initiation of the study

EXCLUSION CRITERIA: None.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: control
Control group: standard care. The iPTH target in this group is 300-540 pg/ml
Drug: standard care
Standard care. Patients allocated to this study arm will be treated with all drugs available for PTH control (at the investigator discretion) to obtain a iPTH of 300-540 pg/ml.
Other Names:
  • Drugs available on the market control iPTH
Experimental: Optimal CKD-MBD control
Optimal CKD-MBD control: in this group the PTH target is150-300 pg/ml to be achieved with a therapeutic algorithm
Drug: Optimal (I. iPTH control: Zemplar®,Mimpara®; phosphorous control: Renvela®, Phoslo®, Osvaren®, Foznol®,Maalox®; calcium control: calcium and vitamin D
Optimal care. Patients allocated to this study arm will be treated with all drugs available for PTH control (at the investigator discretion - see therapeutic algorithm) to obtain a iPTH of less than 300 pg/ml.
Other Names:
  • Drugs available on the market control iPTH

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
percent reduction in weekly ESA consumption to maintain Hb levels within the recommended range 10.0-11.5 g/dl
Time Frame: baseline and after 12 months of followup
Primary objective: to test whether a tighter PTH control to achieve a PTH level lower than 300 pg/ml vs PTH levels between 300-540 pg/ml is associated with a lower ESA dose use to achieve the target Hb of 10.0-11.5 g/dl
baseline and after 12 months of followup

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in iron status and storage.
Time Frame: baseline and after 12 months of followup
Secondary objective: to test whether a tighter PTH control to achieve a PTH level lower than 300 pg/ml vs PTH levels between 300-540 pg/ml is associated with a better iron storage and mobilization.
baseline and after 12 months of followup
Difference in prevalence of cardiac valvular calcification progression detected by echocardiography between groups.
Time Frame: baseline and after 12 months of followup
Secondary objective: to test whether a tighter PTH control to achieve a PTH level lower than 300 pg/ml vs PTH levels between 300-540 pg/ml is associated with cardiac valves deposition and progression attenuation.
baseline and after 12 months of followup
Difference in pulse wave velocity assessed by applanation tonometry between groups.
Time Frame: baseline and after 12 months of followup
Secondary objective: to test whether a tighter PTH control to achieve a PTH level lower than 300 pg/ml vs PTH levels between 300-540 pg/ml is associated with arterial stiffness increase attenuation
baseline and after 12 months of followup
CKD-MBD control
Time Frame: baseline and after 12 months of followup
Secondary objective: to test whether a tighter PTH control to achieve a PTH level lower than 300 pg/ml vs PTH levels between 300-540 pg/ml is associated with a better CKD-MBD control
baseline and after 12 months of followup

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Ospedaliera Sant'Anna

Collaborators

Amgen

Investigators

  • Principal Investigator: Antonio Bellasi, MD, Azienda Ospedaliera Sant'Anna, Ospedale Sant'Anna-Como

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2015

Primary Completion (Anticipated)

December 1, 2016

Study Completion (Anticipated)

March 1, 2017

Study Registration Dates

First Submitted

June 27, 2014

First Submitted That Met QC Criteria

October 23, 2014

First Posted (Estimate)

October 24, 2014

Study Record Updates

Last Update Posted (Estimate)

September 15, 2015

Last Update Submitted That Met QC Criteria

September 12, 2015

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AOSantAnna

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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