Clinical trial NCT00977080: Evaluation of the Effectiveness of Paricalcitol Versus Cinacalcet With Low-Dose Vitamin D
Official title: The IMPACT SHPT Study: Study to Evaluate the Improved Management of iPTH With Paricalcitol-centered Therapy vs. Cinacalcet Therapy With Low-dose Vitamin D in Hemodialysis Patients With Secondary Hyperparathyroidism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Kidney Disease
Secondary Hyperparathyroidism
Hemodialysis
Keywords: Zemplar
paricalcitol
IMPACT SHPT
Hemodialysis
Chronic Kidney Disease Stage 5
Lead sponsor: Abbott
Sponsor class: INDUSTRY
First posted: 2009-09-15
Enrollment: 272
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Evaluates the effectiveness of on-label Paricalcitol versus Cinacalcet with Low-Dose Vitamin D.

Detailed description: During a 4-week washout period, participants stopped taking cinacalcet or other vitamin D receptor activators (VDRAs). (Participants who were naive to cinacalcet or VDRAs did not have to wash out). At randomization, participants entered a 28-week open-label treatment period, during which they received either cinacalcet or paricalcitol. Participants who were assigned to receive paricalcitol were dosed according to the approved label in their respective geographic regions (i.e., IV at sites in the US and Russia and oral at sites in Europe). Supplemental cinacalcet was administered to participants in the paricalcitol arms who developed hypercalcemia (defined as \>= 10.5 mg/dL). The evaluation period was from Weeks 21 to 28.

Eligibility criteria: Inclusion Criteria

1. Male or female patients \>= 18 years old.
2. Patient was diagnosed with Stage 5 chronic kidney disease (CKD) and had been receiving intravenous (IV) or oral vitamin D receptor activators (VDRAs) or cinacalcet during the 8 weeks prior to the screening period or naïve patients who had not received VDRA or cinacalcet within 8 weeks of screening.
3. Patient was on maintenance HD (hemodialysis) 3 times weekly (TIW) for at least 3 months prior to screening and was expected to remain on HD for the duration of the study.
4. For entry into the Pre-Treatment Washout Period (for patients who were not naïve to VDRAs and cinacalcet), the patient had to have screening laboratory values of:

   * iPTH level 130 to 700 pg/mL
   * Serum Total Alkaline Phosphatase level \>= 40 U/L
   * Calcium level \<= 10.0 mg/dL (2.49 mmol/L)
   * Calcium-phosphorus product (CaxP) \<= 75 mg2/dL2 (US) and \<= 70 mg2/dL2 (non-US)

Exclusion Criteria

1. Patient had a history of parathyroidectomy.
2. Patient had a current malignancy (with the exception of basal or squamous cell carcinoma of the skin), or clinically significant liver disease, in the opinion of the investigator.
3. Use of known inhibitors (i.e., ketoconazole) or inducers (i.e., carbamazepine) of cytochrome P450 (including grapefruit and/or grapefruit juice) 3A (CYP3A) or drugs metabolized by cytochrome P450 2D6 (CYP2D6) (e.g., flecainide, vinblastine, thioridazine, and most tricyclic antidepressants) within 2 weeks prior to study drug administration. Commonly used beta blockers such as metoprolol and carvedilol are allowed but are metabolized by CYP2D6; thus, an adjustment to a lower dose may have been required.
4. Patient was known to be human immunodeficiency (HIV) positive.

Primary outcomes:
measure: The Number of Participants Who Achieve a Mean Intact Parathyroid Hormone (iPTH) Value Between 150 to 300 pg/mL During the Evaluation Period (Weeks 21 to 28).
timeFrame: Weeks 21 to 28
Secondary outcomes:
measure: Number of Participants Who Achieve at Least 30% Reduction From Baseline in Intact Parathyroid Hormone (iPTH) as Assessed by the Mean iPTH Obtained During the Evaluation Period (Weeks 21 to 28).
timeFrame: Weeks 21 to 28
measure: Number of Participants Who Achieve at Least 50% Reduction From Baseline in iPTH as Assessed by the Mean iPTH Obtained During the Evaluation Period (Weeks 21 to 28).
timeFrame: Weeks 21 to 28
measure: Analysis of the Number of Participants Who Achieve a Mean iPTH Value Between 150 and 300 pg/mL During the Evaluation Period (Weeks 21 to 28) Using a Cochran-Mantel-Haenszel Test Controlling for IV and Oral Site Randomization Strata
timeFrame: Weeks 21 to 28
measure: Number of Participants With Hypocalcemia Defined as < 8.4 mg/dL and Based on the Mean of at Least 2 Values Obtained During the Evaluation Period (Weeks 21 to 28)
timeFrame: Weeks 21 to 28
measure: Number of Participants With Hypercalcemia Defined as Calcium > 10.5 mg/dL and Based on the Mean of at Least 2 Values Obtained During the Evaluation Period (Weeks 21 to 28)
timeFrame: Weeks 21 to 28
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Site Reference ID/Investigator# 22781
state: Arizona
city: Chula Vista
country: United States
facility: Site Reference ID/Investigator# 24342
state: California
city: Los Angeles
country: United States
facility: Site Reference ID/Investigator# 21142
state: California
city: Los Angeles
country: United States
facility: Site Reference ID/Investigator# 22762
state: California
city: Riverside
country: United States
facility: Site Reference ID/Investigator# 22758
state: California
city: San Diego
country: United States
facility: Site Reference ID/Investigator# 21442
state: California
city: Arvada
country: United States
facility: Site Reference ID/Investigator# 23688
state: Colorado
city: Coral Springs
country: United States
facility: Site Reference ID/Investigator# 21370
state: Florida
city: Hudson
country: United States
facility: Site Reference ID/Investigator# 25902
state: Florida
city: Lauderdale Lakes
country: United States
facility: Site Reference ID/Investigator# 21146
state: Florida
city: Lauderdale Lakes
country: United States
facility: Site Reference ID/Investigator# 26743
state: Florida
city: Miami
country: United States
facility: Site Reference ID/Investigator# 22788
state: Florida
city: Orlando
country: United States
facility: Site Reference ID/Investigator# 22722
state: Florida
city: Tampa
country: United States
facility: Site Reference ID/Investigator# 23147
state: Florida
city: Meridian
country: United States
facility: Site Reference ID/Investigator# 22778
state: Idaho
city: Detroit
country: United States
facility: Site Reference ID/Investigator# 21369
state: Michigan
city: Detroit
country: United States
facility: Site Reference ID/Investigator# 22786
state: Michigan
city: St. Louis
country: United States
facility: Site Reference ID/Investigator# 21144
state: Missouri
city: St. Louis
country: United States
facility: Site Reference ID/Investigator# 21443
state: Missouri
city: Omaha
country: United States
facility: Site Reference ID/Investigator# 21145
state: Nebraska
city: Flushing
country: United States
facility: Site Reference ID/Investigator# 22505
state: New York
city: Toledo
country: United States
facility: Site Reference ID/Investigator# 22759
state: Ohio
city: Lancaster
country: United States
facility: Site Reference ID/Investigator# 22796
state: Pennsylvania
city: Philadelphia
country: United States
facility: Site Reference ID/Investigator# 22770
state: Pennsylvania
city: Aiken
country: United States
facility: Site Reference ID/Investigator# 22772
state: South Carolina
city: Orangeburg
country: United States
facility: Site Reference ID/Investigator# 21147
state: South Carolina
city: Houston
country: United States
facility: Site Reference ID/Investigator# 22982
state: Texas
city: Houston
country: United States
facility: Site Reference ID/Investigator# 21143
state: Texas
city: San Antonio
country: United States
facility: Site Reference ID/Investigator# 22506
state: Texas
city: Bluefield
country: United States
facility: Site Reference ID/Investigator# 22776
state: West Virginia
city: Brno
country: Czech Republic
facility: Site Reference ID/Investigator# 22311
city: Jilemnice
country: Czech Republic
facility: Site Reference ID/Investigator# 22310
city: Usti nad Labem
country: Czech Republic
facility: Site Reference ID/Investigator# 21624
city: Aalborg
country: Denmark
facility: Site Reference ID/Investigator# 22363
city: Copenhagen
country: Denmark
facility: Site Reference ID/Investigator# 23105
city: Fredericia
country: Denmark
facility: Site Reference ID/Investigator# 23909
city: Holstebro
country: Denmark
facility: Site Reference ID/Investigator# 22462
city: Coburg
country: Germany
facility: Site Reference ID/Investigator# 21748
city: Darmstadt
country: Germany
facility: Site Reference ID/Investigator# 33268
city: Duesseldorf
country: Germany
facility: Site Reference ID/Investigator# 35903
city: Frankfurt
country: Germany
facility: Site Reference ID/Investigator# 21742
city: Heilbronn
country: Germany
facility: Site Reference ID/Investigator# 21744
city: Luedenscheid
country: Germany
facility: Site Reference ID/Investigator# 21368
city: Athens
country: Greece
facility: Site Reference ID/Investigator# 22362
city: Thessaloniki
country: Greece
facility: Site Reference ID/Investigator# 38970
city: Thessaloniki
country: Greece
facility: Site Reference ID/Investigator# 22322
city: Thessaloniki
country: Greece
facility: Site Reference ID/Investigator# 22463
city: Thessaloniki
country: Greece
facility: Site Reference ID/Investigator# 22323
city: Thessaloniki
country: Greece
facility: Site Reference ID/Investigator# 39262
city: Bergamo
country: Italy
facility: Site Reference ID/Investigator# 22312
city: Genova
country: Italy
facility: Site Reference ID/Investigator# 21746
city: Lucca
country: Italy
facility: Site Reference ID/Investigator# 39180
city: Milan
country: Italy
facility: Site Reference ID/Investigator# 22314
city: Pavia
country: Italy
facility: Site Reference ID/Investigator# 21367
city: Pesaro
country: Italy
facility: Site Reference ID/Investigator# 21745
city: Alkmaar
country: Netherlands
facility: Site Reference ID/Investigator# 21842
city: Delft
country: Netherlands
facility: Site Reference ID/Investigator# 22309
city: Dordrecht
country: Netherlands
facility: Site Reference ID/Investigator# 21843
city: Beja
country: Portugal
facility: Site Reference ID/Investigator# 38903
city: Faro
country: Portugal
facility: Site Reference ID/Investigator# 38531
city: Lisbon
country: Portugal
facility: Site Reference ID/Investigator# 22464
city: Vila Franca de Xira
country: Portugal
facility: Site Reference ID/Investigator# 23910
city: Moscow
country: Russian Federation
facility: Site Reference ID/Investigator# 24643
city: Moscow
country: Russian Federation
facility: Site Reference ID/Investigator# 24642
city: Barcelona
country: Spain
facility: Site Reference ID/Investigator# 21361
city: Cordoba
country: Spain
facility: Site Reference ID/Investigator# 21364
city: L'Hospitalet, Barcelona
country: Spain
facility: Site Reference ID/Investigator# 22366
city: Madrid
country: Spain
facility: Site Reference ID/Investigator# 38343
city: Madrid
country: Spain
facility: Site Reference ID/Investigator# 21362
city: Palma de Mallorca
country: Spain
facility: Site Reference ID/Investigator# 21363
city: Pamplona
country: Spain
facility: Site Reference ID/Investigator# 22367
city: Puerto de la Cruz
country: Spain
facility: Site Reference ID/Investigator# 38462
city: Seville
country: Spain
facility: Site Reference ID/Investigator# 21365
city: Linkoping
country: Sweden
facility: Site Reference ID/Investigator# 23913
city: Stockholm
country: Sweden
facility: Site Reference ID/Investigator# 23782
city: Uppsala
country: Sweden
facility: Site Reference ID/Investigator# 22364
city: Birmingham
country: United Kingdom
facility: Site Reference ID/Investigator# 23912
city: Coventry
country: United Kingdom
facility: Site Reference ID/Investigator# 21747
city: London
country: United Kingdom
facility: Site Reference ID/Investigator# 23102
city: London
country: United Kingdom
facility: Site Reference ID/Investigator# 23104
city: Manchester
country: United Kingdom
facility: Site Reference ID/Investigator# 23103
city: Omagh, Northern Ireland
country: United Kingdom
facility: Site Reference ID/Investigator# 41982
city: Sheffield
country: United Kingdom
facility: Site Reference ID/Investigator# 40222
Study officials:
affiliation: Abbott
name: Samina Khan, MD
role: STUDY_DIRECTOR
References:
citation: Cozzolino M, Ketteler M, Martin KJ, Sharma A, Goldsmith D, Khan S. Paricalcitol- or cinacalcet-centred therapy affects markers of bone mineral disease in patients with secondary hyperparathyroidism receiving haemodialysis: results of the IMPACT-SHPT study. Nephrol Dial Transplant. 2014 Apr;29(4):899-905. doi: 10.1093/ndt/gfu011. Epub 2014 Feb 4.
citation: Sharma A, Marshall TS, Khan SS, Johns B. Cost effectiveness of paricalcitol versus cinacalcet with low-dose vitamin D for management of secondary hyperparathyroidism in haemodialysis patients in the USA. Clin Drug Investig. 2014 Feb;34(2):107-15. doi: 10.1007/s40261-013-0151-4.
citation: Ketteler M, Martin KJ, Wolf M, Amdahl M, Cozzolino M, Goldsmith D, Sharma A, Marx S, Khan S. Paricalcitol versus cinacalcet plus low-dose vitamin D therapy for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis: results of the IMPACT SHPT study. Nephrol Dial Transplant. 2012 Aug;27(8):3270-8. doi: 10.1093/ndt/gfs018. Epub 2012 Mar 2.