Paricalcitol Oral Therapy in Predialysis CKD Patients. The Greek Experience (PROTECT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01083186
First received: February 20, 2010
Last updated: March 11, 2013
Last verified: March 2013
  Purpose

The purpose of this study is to obtain data on the use of Zemplar (paricalcitol) capsules in real-life clinical practice in predialysis patients with chronic kidney disease (CKD) and secondary hyperparathyroidism.


Condition
Chronic Kidney Failure
Secondary Hyperparathyroidism

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Paricalcitol Oral Therapy in Predialysis CKD Patients. The Greek Experience

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Intact Parathormone (iPTH) Changes During the Study Time-Points for Overall Study Population [ Time Frame: Baseline, Enrollment Visit, Month 3, Month 6, Month 9, Month 12 ] [ Designated as safety issue: No ]
    iPTH levels before and after oral paricalcitol treatment onset were recorded at each study visit, and corresponding changes were calculated for the overall study population.

  • Intact Parathormone (iPTH) Changes During the Study Time-Points for Subpopulation of Renal Transplanted Participants [ Time Frame: Baseline, Enrollment Visit, Month 3, Month 6, Month 9, Month 12 ] [ Designated as safety issue: No ]
    iPTH levels before and after oral paricalcitol treatment onset were recorded at each study visit, and corresponding changes were calculated for the subpopulation of renal transplanted participants.


Secondary Outcome Measures:
  • Median Time to Attain the First Lower Intact Parathormone (iPTH) Levels [ Time Frame: Measured from start of study, up to a maximum of 12 months ] [ Designated as safety issue: No ]
    The time to attain the first lower iPTH levels was considered as the time from the date of oral paricalcitol treatment onset until the date when any of the following conditions were initially met: a 30% reduction from iPTH levels prior to treatment onset had been achieved, for patients who were still outside the target range; or iPTH levels equal or lower to the upper limit of the target range according to Kidney Disease Quality Outcome Initiative (K/DOQI) guidelines (CKD Stage 3: ≤ 70 pg/mL; CKD Stage 4: ≤ 110 pg/mL; CKD Stage 5: ≤ 300 pg/mL).

  • Mean Duration of Effect Sustainability (Months) [ Time Frame: Measured from start of study, up to a maximum of 12 months ] [ Designated as safety issue: No ]
    The effect was considered sustainable if: the participant's intact parathormone (iPTH) value remained equal or lower to the upper limit of the target range according to Kidney Disease Quality Outcome Initiative (K/DOQI) guidelines (CKD Stage 3: ≤ 70 pg/mL; CKD Stage 4: ≤ 110 pg/mL); or iPTH levels continued to decrease 30% from the previous available measurement.

  • Distribution of Participants by Achievement of Intact Parathormone (iPTH) Levels Within the Target Range [ Time Frame: Enrollment Visit, Month 3, Month 6, Month 9, Month 12 ] [ Designated as safety issue: No ]
    Number of participants with iPTH levels within the target range of Kidney Disease Quality Outcome Initiative (K/DOQI) treatment guidelines at each study measurement after oral paricalcitol treatment onset. K/DOQI treatment guidelines: CKD Stage 3: 35-70 pg/mL; CKD Stage 4: 70-110 pg/mL during a 12-month period of treatment with oral paricalcitol.

  • Number of Participants With Serum Calcium Level Abnormalities [ Time Frame: Baseline, Enrollment Visit, Month 6, Month 12 ] [ Designated as safety issue: Yes ]
    Normal serum calcium range was 8.4-10.2 mg/dL.

  • Number of Participants With Serum Phosphorus Level Abnormalities [ Time Frame: Baseline, Enrollment Visit, Month 6, Month 12 ] [ Designated as safety issue: Yes ]
    Normal serum phosphorus range was 2.7-4.6 mg/dL.

  • Change in Dipstick Albuminuria Grade From Baseline to Month 6 [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: Yes ]
    The values "-, Trace, +, ++, and +++" are taken directly from the dipstick measurements, and represent a range from none to highest albuminuria. Data presented shows the number of participants with each value both at Baseline and at Month 6.

  • Change in Dipstick Albuminuria Grade From Baseline to Month 12 [ Time Frame: Baseline, Month 12 ] [ Designated as safety issue: Yes ]
    The values "-, Trace, +, ++, and +++" are taken directly from the dipstick measurements, and represent a range from none to highest albuminuria. Data presented shows the number of participants with each value both at Baseline and at Month 6.

  • Glycosylated Hemoglobin A1c (HbA1c) Values Throughout the Study [ Time Frame: Baseline, Enrollment Visit, Month 6, Month 12 ] [ Designated as safety issue: Yes ]
    The HbA1c normal range was 4.3-6.1%.

  • Non-serious Adverse Events (nSAEs) and Serious Adverse Events (SAEs) [ Time Frame: From time of enrollment throughout the study up to 12 months for nSAEs. SAEs from time of enrollment throughout the study up to + 30 days after end of study. ] [ Designated as safety issue: Yes ]
    In order to establish the safety profile of oral paricalcitol in daily clinical practice, non-serious adverse events (nSAEs) and serious adverse events (SAEs) were collected during the course of the study. An adverse event (AE) is defined as any untoward medical occurrence in a patient, which does not necessarily have a causal relationship with their treatment. If an adverse event meets any of the following criteria, it is considered a serious adverse event (SAE): results in death or is life-threatening, results in admission or prolongation of hospitalization, is a congenital anomaly or persistent or significant disability/incapacity or is an important medical event requiring medical or surgical intervention to prevent any of the outcomes listed above. Please see Adverse Events section below for more details.

  • Distribution of Participants by Chronic Kidney Disease (CKD) Stage Throughout Study [ Time Frame: Baseline, Enrollment Visit, Month 3, Month 6, Month 9, Month 12 ] [ Designated as safety issue: No ]
    Change in CKD stage throughout the study period was assessed by the estimated glomerular filtration rate (eGFR) levels recorded by the physicians at each study time point. Classification of eGFR into CKD stages as follows: CKD stage 2: 60-89 mL/min/1.73m^2; CKD stage 3: 30-59 mL/min/1.73m^2; CKD stage 4: 15-29 mL/min/1.73m^2; CKD stage 5: <15 mL/min/1.73/m^2. Table presents the number of participants by stage at each study visit.

  • Estimated Glomerular Filtration Rate (eGFR) Values Throughout the Study [ Time Frame: Baseline, Enrollment Visit, Month 3, Month 6, Month 9, Month 12 ] [ Designated as safety issue: Yes ]
    The eGFR normal range was 90-120 mL/min/1.73m^2.

  • Change From Baseline in Alanine Aminotransferase (ALT) Levels at Months 6 and 12 [ Time Frame: Baseline, Month 6, Month 12 ] [ Designated as safety issue: Yes ]
    The alanine aminotransferase normal range was 11-43 IU/L.

  • Change From Baseline in Aspartate Aminotransferase (AST) Levels at Months 6 and 12 [ Time Frame: Baseline, Month 6, Month 12 ] [ Designated as safety issue: Yes ]
    The aspartate aminotransferase normal range was 11-38 IU/L.

  • Change From Baseline in Creatinine Levels at Months 6 and 12 [ Time Frame: Baseline, Month 6, Month 12 ] [ Designated as safety issue: Yes ]
    The creatinine normal range was 0.6-1.4 mg/dL.

  • Change From Baseline in Urea Levels at Months 6 and 12 [ Time Frame: Baseline, Month 6, Month 12 ] [ Designated as safety issue: Yes ]
    The urea normal range was 10-50 mg/dL.

  • Change From Baseline in Alkaline Phosphatase (ALP) Levels at Months 6 and 12 [ Time Frame: Baseline, Month 6, Month 12 ] [ Designated as safety issue: Yes ]
    The alkaline phosphatase normal range was 40-129 IU/L.

  • Change From Enrollment in Total Cholesterol Levels at Months 6 and 12 [ Time Frame: Enrollment, Month 6, Month 12 ] [ Designated as safety issue: Yes ]
    The total cholesterol normal range was 130-200 mg/dL.

  • Change From Enrollment in Triglyceride Levels at Months 6 and 12 [ Time Frame: Enrollment, Month 6, Month 12 ] [ Designated as safety issue: Yes ]
    The normal range for triglycerides was 0-200 mg/dL.

  • Change From Enrollment in Low Density Lipoprotein Cholesterol (LDL-C) Levels at Months 6 and 12 [ Time Frame: Enrollment, Month 6, Month 12 ] [ Designated as safety issue: Yes ]
    The LDL-C normal range was 0-150 mg/dL.

  • Change From Enrollment in High Density Lipoprotein Cholesterol (HDL-C) Levels at Months 6 and 12 [ Time Frame: Enrollment, Month 6, Month 12 ] [ Designated as safety issue: Yes ]
    The HDL-C normal range was 35-90 mg/dL.

  • Change From Baseline in C-Reactive Protein (CRP) Levels at Months 6 and 12 [ Time Frame: Baseline, Month 6, Month 12 ] [ Designated as safety issue: Yes ]
    The CRP normal range was 0-0.6 mg/dL.

  • Homocysteine Values Throughout the Study [ Time Frame: Baseline, Enrollment Visit, Month 6, Month 12 ] [ Designated as safety issue: Yes ]
    The homocysteine normal range 3.5-20 μmol/L.


Enrollment: 500
Study Start Date: June 2009
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
Chronic Kidney Disease (CKD), Secondary Hyperpathyroidism
Participants with chronic kidney disease stage 3-5 with secondary hyperparathyroidism, who were prescribed oral paricalcitol according to the approved Summary of Product Characteristics (SmPC)

Detailed Description:

This was a single arm, open, multicenter, non-interventional, post marketing observational study, which has been conducted in 24 sites in Greece, under normal clinical practice and as per the locally approved Summary of Product Characteristics (SmPC) of study medication (oral paricalcitol). Eligible patients were followed up for a 12-month period after enrollment. All study activities were consistent with European Union (EU) directive 2001/20/EC section for non-interventional studies.

In this study, paricalcitol was prescribed on an on-label basis in an everyday setting to observe drug actions in a distinct geography (Greece with > 250 days/year of sunny days) as well as in a significant subpopulation (Chronic Kidney Disease [CKD] stages 3-5 transplanted patients). Dose tolerability, treatment effects, as well as maintenance of results were registered for a 12-month period in order to obtain experience in the long term use of paricalcitol capsules. Furthermore, in centers where additional blood parameters were examined as part of clinical routine, these were recorded and analyzed.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Patients from 24 hospital-based specialty, nephrology clinics in Greece

Criteria

Inclusion Criteria:

  • Patients with secondary hyperparathyroidism in the presence of chronic kidney disease stage 3, 4 or 5 treated with Zemplar (paricalcitol) oral for at least 1 month prior to study enrollment
  • Male and female (not pregnant or not planning to be pregnant in the next 12 months) patients > 18 years of age
  • Signed informed consent by subject
  • Hypertensive and diabetic subjects must be on an optimal and steady medication regimen for more than 30 days

Exclusion Criteria:

  • Contraindications listed in the Summary of Product Characteristics for Zemplar capsules apply (Appendix I and II)
  • Parathormone value of > 1000 pg/mL (sign of tertiary hyperparathyroidism)
  • Treatment with Vitamin D within the last 1 month prior to inclusion into the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01083186

Locations
Greece
Site Reference ID/Investigator# 47002
Arta, Greece, 47100
Site Reference ID/Investigator# 38257
Athens, Greece, 11526
Site Reference ID/Investigator# 47003
Athens, Greece, 11526
Site Reference ID/Investigator# 27492
Athens, Greece, 115 27
Site Reference ID/Investigator# 43772
Athens, Greece, 115 21
Site Reference ID/Investigator# 43773
Athens, Greece, 17237
Site Reference ID/Investigator# 27489
Athens, Greece, 11528
Site Reference ID/Investigator# 47004
Athens, Greece, 11527
Site Reference ID/Investigator# 27497
Athens, Greece, 11527
Site Reference ID/Investigator# 43769
Athens, Greece, 115 27
Site Reference ID/Investigator# 27495
Athens, Greece, 16673
Site Reference ID/Investigator# 27498
Haidari, Athens, Greece, 12462
Site Reference ID/Investigator# 38259
Ioannina, Greece, 45500
Site Reference ID/Investigator# 43771
Larissa, Greece, 41223
Site Reference ID/Investigator# 22121
Larissa, Greece, 411 10
Site Reference ID/Investigator# 43767
Maroussi Athens, Greece, 15123
Site Reference ID/Investigator# 27496
Nikaia, Greece, 18454
Site Reference ID/Investigator# 43768
North Ionia, Athens, Greece, 142 33
Site Reference ID/Investigator# 27491
Piraeus, Greece, 18536
Site Reference ID/Investigator# 43770
Thessaloniki, Greece, 570 01
Site Reference ID/Investigator# 39839
Thessaloniki, Greece
Site Reference ID/Investigator# 38255
Thessaloniki, Greece, 56403
Site Reference ID/Investigator# 27494
Thessaloniki, Greece, 546 36
Site Reference ID/Investigator# 27493
Thessaloniki, Greece, 54636
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Christos Argyropoulos, MD AbbVie Pharmaceuticals S.A.
  More Information

Additional Information:
No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01083186     History of Changes
Other Study ID Numbers: P11-978
Study First Received: February 20, 2010
Results First Received: January 31, 2013
Last Updated: March 11, 2013
Health Authority: Greece: National Organization of Medicines

Keywords provided by AbbVie:
Secondary Hyperparathyroidism
Chronic Kidney Failure

Additional relevant MeSH terms:
Hyperparathyroidism
Hyperparathyroidism, Secondary
Kidney Failure, Chronic
Renal Insufficiency
Endocrine System Diseases
Kidney Diseases
Parathyroid Diseases
Renal Insufficiency, Chronic
Urologic Diseases

ClinicalTrials.gov processed this record on October 23, 2014