Paricalcitol Oral Therapy in Predialysis CKD Patients. The Greek Experience

Secondary Hyperparathyroidism Clinical Trial

— PROTECT  

Official title:

Paricalcitol Oral Therapy in Predialysis CKD Patients. The Greek Experience

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01083186
• Other study ID #: P11-978
• Status: Completed
• Phase: N/A
• First received: February 20, 2010
• Last updated: March 11, 2013
• Start date: June 2009
• Est. completion date: January 2012

Study information

• Verified date: March 2013
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Health authority: Greece: National Organization of Medicines
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 500
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Chronic Kidney Failure
• Hyperparathyroidism
• Hyperparathyroidism, Secondary
• Kidney Failure, Chronic
• Renal Insufficiency
• Secondary Hyperparathyroidism

Locations

Country	Name	City	State
Greece	Site Reference ID/Investigator# 47002	Arta
Greece	Site Reference ID/Investigator# 27489	Athens
Greece	Site Reference ID/Investigator# 27492	Athens
Greece	Site Reference ID/Investigator# 27495	Athens
Greece	Site Reference ID/Investigator# 27497	Athens
Greece	Site Reference ID/Investigator# 38257	Athens
Greece	Site Reference ID/Investigator# 43769	Athens
Greece	Site Reference ID/Investigator# 43772	Athens
Greece	Site Reference ID/Investigator# 43773	Athens
Greece	Site Reference ID/Investigator# 47003	Athens
Greece	Site Reference ID/Investigator# 47004	Athens
Greece	Site Reference ID/Investigator# 27498	Haidari, Athens
Greece	Site Reference ID/Investigator# 38259	Ioannina
Greece	Site Reference ID/Investigator# 22121	Larissa
Greece	Site Reference ID/Investigator# 43771	Larissa
Greece	Site Reference ID/Investigator# 43767	Maroussi Athens
Greece	Site Reference ID/Investigator# 27496	Nikaia
Greece	Site Reference ID/Investigator# 43768	North Ionia, Athens
Greece	Site Reference ID/Investigator# 27491	Piraeus
Greece	Site Reference ID/Investigator# 27493	Thessaloniki
Greece	Site Reference ID/Investigator# 27494	Thessaloniki
Greece	Site Reference ID/Investigator# 38255	Thessaloniki
Greece	Site Reference ID/Investigator# 39839	Thessaloniki
Greece	Site Reference ID/Investigator# 43770	Thessaloniki

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie (prior sponsor, Abbott)

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intact Parathormone (iPTH) Changes During the Study Time-Points for Overall Study Population	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.	Baseline, Enrollment Visit, Month 3, Month 6, Month 9, Month 12	No
Primary	Intact Parathormone (iPTH) Changes During the Study Time-Points for Subpopulation of Renal Transplanted Participants	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.	Baseline, Enrollment Visit, Month 3, Month 6, Month 9, Month 12	No
Secondary	Median Time to Attain the First Lower Intact Parathormone (iPTH) Levels	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).	Measured from start of study, up to a maximum of 12 months	No
Secondary	Mean Duration of Effect Sustainability (Months)	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.	Measured from start of study, up to a maximum of 12 months	No
Secondary	Distribution of Participants by Achievement of Intact Parathormone (iPTH) Levels Within the Target Range	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.	Enrollment Visit, Month 3, Month 6, Month 9, Month 12	No
Secondary	Number of Participants With Serum Calcium Level Abnormalities	Normal serum calcium range was 8.4-10.2 mg/dL.	Baseline, Enrollment Visit, Month 6, Month 12	Yes
Secondary	Number of Participants With Serum Phosphorus Level Abnormalities	Normal serum phosphorus range was 2.7-4.6 mg/dL.	Baseline, Enrollment Visit, Month 6, Month 12	Yes
Secondary	Change in Dipstick Albuminuria Grade From Baseline to Month 6	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.	Baseline, Month 6	Yes
Secondary	Change in Dipstick Albuminuria Grade From Baseline to Month 12	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.	Baseline, Month 12	Yes
Secondary	Glycosylated Hemoglobin A1c (HbA1c) Values Throughout the Study	The HbA1c normal range was 4.3-6.1%.	Baseline, Enrollment Visit, Month 6, Month 12	Yes
Secondary	Non-serious Adverse Events (nSAEs) and Serious Adverse Events (SAEs)	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.	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.	Yes
Secondary	Distribution of Participants by Chronic Kidney Disease (CKD) Stage Throughout Study	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.	Baseline, Enrollment Visit, Month 3, Month 6, Month 9, Month 12	No
Secondary	Estimated Glomerular Filtration Rate (eGFR) Values Throughout the Study	The eGFR normal range was 90-120 mL/min/1.73m^2.	Baseline, Enrollment Visit, Month 3, Month 6, Month 9, Month 12	Yes
Secondary	Change From Baseline in Alanine Aminotransferase (ALT) Levels at Months 6 and 12	The alanine aminotransferase normal range was 11-43 IU/L.	Baseline, Month 6, Month 12	Yes
Secondary	Change From Baseline in Aspartate Aminotransferase (AST) Levels at Months 6 and 12	The aspartate aminotransferase normal range was 11-38 IU/L.	Baseline, Month 6, Month 12	Yes
Secondary	Change From Baseline in Creatinine Levels at Months 6 and 12	The creatinine normal range was 0.6-1.4 mg/dL.	Baseline, Month 6, Month 12	Yes
Secondary	Change From Baseline in Urea Levels at Months 6 and 12	The urea normal range was 10-50 mg/dL.	Baseline, Month 6, Month 12	Yes
Secondary	Change From Baseline in Alkaline Phosphatase (ALP) Levels at Months 6 and 12	The alkaline phosphatase normal range was 40-129 IU/L.	Baseline, Month 6, Month 12	Yes
Secondary	Change From Enrollment in Total Cholesterol Levels at Months 6 and 12	The total cholesterol normal range was 130-200 mg/dL.	Enrollment, Month 6, Month 12	Yes
Secondary	Change From Enrollment in Triglyceride Levels at Months 6 and 12	The normal range for triglycerides was 0-200 mg/dL.	Enrollment, Month 6, Month 12	Yes
Secondary	Change From Enrollment in Low Density Lipoprotein Cholesterol (LDL-C) Levels at Months 6 and 12	The LDL-C normal range was 0-150 mg/dL.	Enrollment, Month 6, Month 12	Yes
Secondary	Change From Enrollment in High Density Lipoprotein Cholesterol (HDL-C) Levels at Months 6 and 12	The HDL-C normal range was 35-90 mg/dL.	Enrollment, Month 6, Month 12	Yes
Secondary	Change From Baseline in C-Reactive Protein (CRP) Levels at Months 6 and 12	The CRP normal range was 0-0.6 mg/dL.	Baseline, Month 6, Month 12	Yes
Secondary	Homocysteine Values Throughout the Study	The homocysteine normal range 3.5-20 µmol/L.	Baseline, Enrollment Visit, Month 6, Month 12	Yes

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