Optimal Anemia Treatment in End Stage Renal Disease (ERSD) (OPTIMAL)
Primary Purpose
Hyperparathyroidism, Secondary
Status
Unknown status
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
standard care
Optimal (I. iPTH control: Zemplar®,Mimpara®; phosphorous control: Renvela®, Phoslo®, Osvaren®, Foznol®,Maalox®; calcium control: calcium and vitamin D
Sponsored by
About this trial
This is an interventional supportive care trial for Hyperparathyroidism, Secondary focused on measuring Hyperparathyroidism, Secondary, Anemia, Vascular Stiffness, Vascular Calcification
Eligibility Criteria
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.
Sites / Locations
- Azienda Ospedaliera Sant'AnnaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
control
Optimal CKD-MBD control
Arm Description
Control group: standard care. The iPTH target in this group is 300-540 pg/ml
Optimal CKD-MBD control: in this group the PTH target is150-300 pg/ml to be achieved with a therapeutic algorithm
Outcomes
Primary Outcome Measures
percent reduction in weekly ESA consumption to maintain Hb levels within the recommended range 10.0-11.5 g/dl
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
Secondary Outcome Measures
Change in iron status and storage.
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.
Difference in prevalence of cardiac valvular calcification progression detected by echocardiography between groups.
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.
Difference in pulse wave velocity assessed by applanation tonometry between groups.
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
CKD-MBD control
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
Full Information
NCT ID
NCT02273570
First Posted
June 27, 2014
Last Updated
September 12, 2015
Sponsor
Azienda Ospedaliera Sant'Anna
Collaborators
Amgen
1. Study Identification
Unique Protocol Identification Number
NCT02273570
Brief Title
Optimal Anemia Treatment in End Stage Renal Disease (ERSD)
Acronym
OPTIMAL
Official Title
Single-center, Open-label, Randomized Study of Anemia Management Improvement in End Stage Renal Disease (ESRD) Patients With Secondary Hyperparathyroidism
Study Type
Interventional
2. Study Status
Record Verification Date
September 2015
Overall Recruitment Status
Unknown status
Study Start Date
March 2015 (undefined)
Primary Completion Date
December 2016 (Anticipated)
Study Completion Date
March 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Azienda Ospedaliera Sant'Anna
Collaborators
Amgen
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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)
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperparathyroidism, Secondary
Keywords
Hyperparathyroidism, Secondary, Anemia, Vascular Stiffness, Vascular Calcification
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
control
Arm Type
Active Comparator
Arm Description
Control group: standard care. The iPTH target in this group is 300-540 pg/ml
Arm Title
Optimal CKD-MBD control
Arm Type
Experimental
Arm Description
Optimal CKD-MBD control: in this group the PTH target is150-300 pg/ml to be achieved with a therapeutic algorithm
Intervention Type
Drug
Intervention Name(s)
standard care
Other Intervention Name(s)
Drugs available on the market control iPTH
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Optimal (I. iPTH control: Zemplar®,Mimpara®; phosphorous control: Renvela®, Phoslo®, Osvaren®, Foznol®,Maalox®; calcium control: calcium and vitamin D
Other Intervention Name(s)
Drugs available on the market control iPTH
Intervention Description
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.
Primary Outcome Measure Information:
Title
percent reduction in weekly ESA consumption to maintain Hb levels within the recommended range 10.0-11.5 g/dl
Description
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
Time Frame
baseline and after 12 months of followup
Secondary Outcome Measure Information:
Title
Change in iron status and storage.
Description
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.
Time Frame
baseline and after 12 months of followup
Title
Difference in prevalence of cardiac valvular calcification progression detected by echocardiography between groups.
Description
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.
Time Frame
baseline and after 12 months of followup
Title
Difference in pulse wave velocity assessed by applanation tonometry between groups.
Description
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
Time Frame
baseline and after 12 months of followup
Title
CKD-MBD control
Description
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
Time Frame
baseline and after 12 months of followup
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Antonio Bellasi, MD
Email
antonio.bellasi@hsacomo.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonio Bellasi, MD
Organizational Affiliation
Azienda Ospedaliera Sant'Anna, Ospedale Sant'Anna-Como
Official's Role
Principal Investigator
Facility Information:
Facility Name
Azienda Ospedaliera Sant'Anna
City
San Fermo della battaglia (CO)
ZIP/Postal Code
22020
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Simona Urbano
Phone
+39.031.585.8947
Email
comitato.etica@hsacomo.org
First Name & Middle Initial & Last Name & Degree
Antonio Bellasi, MD
First Name & Middle Initial & Last Name & Degree
Claudio Minoretti, MD
12. IPD Sharing Statement
Citations:
PubMed Identifier
19229819
Citation
Capuano A, Serio V, Pota A, Memoli B, Andreucci VE. Beneficial effects of better control of secondary hyperparathyroidism with paricalcitol in chronic dialysis patients. J Nephrol. 2009 Jan-Feb;22(1):59-68.
Results Reference
background
PubMed Identifier
17699349
Citation
Ebben JP, Gilbertson DT, Foley RN, Collins AJ. Hemoglobin level variability: associations with comorbidity, intercurrent events, and hospitalizations. Clin J Am Soc Nephrol. 2006 Nov;1(6):1205-10. doi: 10.2215/CJN.01110306. Epub 2006 Sep 6.
Results Reference
background
PubMed Identifier
16105069
Citation
Fishbane S, Berns JS. Hemoglobin cycling in hemodialysis patients treated with recombinant human erythropoietin. Kidney Int. 2005 Sep;68(3):1337-43. doi: 10.1111/j.1523-1755.2005.00532.x.
Results Reference
background
PubMed Identifier
18045862
Citation
Gilbertson DT, Ebben JP, Foley RN, Weinhandl ED, Bradbury BD, Collins AJ. Hemoglobin level variability: associations with mortality. Clin J Am Soc Nephrol. 2008 Jan;3(1):133-8. doi: 10.2215/CJN.01610407. Epub 2007 Nov 28.
Results Reference
background
PubMed Identifier
12500228
Citation
Lacson E Jr, Ofsthun N, Lazarus JM. Effect of variability in anemia management on hemoglobin outcomes in ESRD. Am J Kidney Dis. 2003 Jan;41(1):111-24. doi: 10.1053/ajkd.2003.50030.
Results Reference
background
PubMed Identifier
15211443
Citation
Pisoni RL, Bragg-Gresham JL, Young EW, Akizawa T, Asano Y, Locatelli F, Bommer J, Cruz JM, Kerr PG, Mendelssohn DC, Held PJ, Port FK. Anemia management and outcomes from 12 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis. 2004 Jul;44(1):94-111. doi: 10.1053/j.ajkd.2004.03.023.
Results Reference
background
PubMed Identifier
19644521
Citation
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2009 Aug;(113):S1-130. doi: 10.1038/ki.2009.188.
Results Reference
background
PubMed Identifier
14520607
Citation
National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003 Oct;42(4 Suppl 3):S1-201. No abstract available.
Results Reference
background
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Optimal Anemia Treatment in End Stage Renal Disease (ERSD)
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