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EVOLVE: Difference between revisions
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*** Atrial fibrillation: 10% | *** Atrial fibrillation: 10% | ||
====Biochemical==== | ====Biochemical==== | ||
* Hemoglobin: 11.8 g/dL | * Hemoglobin: 11.8 g/dL | ||
* BUN: 61.9 mg/dL | * BUN: 61.9 mg/dL | ||
* Creatinine: 10.1 mg/dL | * Creatinine: 10.1 mg/dL | ||
* Dialysis dose ≥1.2 spKt/V or ≥65 URR | * Dialysis dose ≥1.2 spKt/V or ≥65 URR: 85.1% | ||
* Serum calcium: 9.8 mg/dL | * Serum calcium: 9.8 mg/dL | ||
* Serum phospohorus: 6.5 mg/dL | * Serum phospohorus: 6.5 mg/dL | ||
* Serum | * Serum Ca × P: 63.2 mg²/dL² | ||
* Serum | * Serum potassium: 5.1 mEq/L | ||
* PTH: 691.8 pg/mL | * PTH: 691.8 pg/mL | ||
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** Starting dose of 30 mg/d | ** Starting dose of 30 mg/d | ||
** Eligible for dose escalation once every 4 weeks during a 20 week escalation phase, or every 8 weeks during followup | ** Eligible for dose escalation once every 4 weeks during a 20 week escalation phase, or every 8 weeks during followup | ||
** Dose | ** Dose escalated to achieve PTH <300 pg/mL and calcium <8 mg/dL | ||
* Placebo group received | * Placebo group received same doses and dosing protocol as treatment group | ||
==Outcomes== | ==Outcomes== | ||
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===Primary Outcome=== | ===Primary Outcome=== | ||
; Time to death or first nonfatal CV event | ; Time to death or first nonfatal CV event | ||
: 48.2% vs. 49.2% (HR | : 48.2% vs. 49.2% (HR 0.93; 95% CI 0.85-1.02; P=0.11) | ||
: ''After adjustment for baseline characteristics: HR 0.88 (95% CI 0.79-0.97; P=0.008) | : ''After adjustment for baseline characteristics: HR 0.88 (95% CI 0.79-0.97; P=0.008) | ||
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: HR 0.83 (95% CI 0.73-0.96; P=0.009) | : HR 0.83 (95% CI 0.73-0.96; P=0.009) | ||
===Adverse Events===< | ===Adverse Events=== | ||
; Any AE: 93% vs. 91% (P<0.001) | |||
; Serious AEs: 69% vs. 70% | |||
; Treatment-related serious AEs: 3.6% vs. 2.3% (P=0.049) | |||
; Convulsions: 2.5% vs. 0.8% | |||
; Hypocalcemia: 12.4% vs. 1.7% (P<0.001) | |||
; Hypersensitivity reaction: 9.4% vs. 8.3% | |||
; Nervous system disorder: 36.7% vs. 30.5% (P<0.001) | |||
; Nausea 29.1% vs. 15.5% (P<0.001) | |||
; Vomiting: 25.6% vs. 13.7% (P<0.001) | |||
; Diarrhea: 20.5% vs. 18.7% | |||
==Criticisms== | |||
==Criticisms== | |||
* Age-adjusted HR results in statistically significant results for primary outcome, but was not defined as the primary endpoint | * Age-adjusted HR results in statistically significant results for primary outcome, but was not defined as the primary endpoint | ||
** Patients one year older in cinacalcet group; older age known to increase mortality in dialysis patients | ** Patients one year older in cinacalcet group; older age known to increase mortality in dialysis patients | ||
* Censored analysis results in statistically significant results for primary outcome, but was not defined as the primary endpoint | * Censored analysis results in statistically significant results for primary outcome, but was not defined as the primary endpoint | ||
* High drug discontinuation rates (66.7% vs. 70.5%) | * High drug discontinuation rates (66.7% vs. 70.5%) | ||
* High | * High crossover (use of commercial cinacalcet) in placebo group (19.8%) | ||
* Under the initial assumption of a 20% treatment effect, the presumed study power of 90% to 54% secondary to crossovers and drop-outs<ref name="moe">[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3983668/pdf/nihms568937.pdf Moe SM, Thadhani R. "What have we learned about CKD-MBD From the EVOLVE and PRIMO trials?" ''Curr Opin Nephrol Hypertens''. 2013; 22(6): 651–655.]</ref> | * Under the initial assumption of a 20% treatment effect, the presumed study power of 90% to 54% secondary to crossovers and drop-outs<ref name="moe">[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3983668/pdf/nihms568937.pdf Moe SM, Thadhani R. "What have we learned about CKD-MBD From the EVOLVE and PRIMO trials?" ''Curr Opin Nephrol Hypertens''. 2013; 22(6): 651–655.]</ref> | ||
* Combination of atherosclerotic and non-atherosclerotic cardiovascular endpoints | * Combination of atherosclerotic and non-atherosclerotic cardiovascular endpoints | ||
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<references> | <references> | ||
<ref name="kdigo">[http://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO%20CKD-MBD%20GL%20KI%20Suppl%20113.pdf 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 International.'' 2009; 76 (Suppl 113): S1–S130.]</ref> | <ref name="kdigo">[http://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO%20CKD-MBD%20GL%20KI%20Suppl%20113.pdf 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 International.'' 2009; 76 (Suppl 113): S1–S130.]</ref> | ||
<ref name="design">[http:// | <ref name="design">[http://cjasn.asnjournals.org/content/2/5/898.full Chertow GM, et al. Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE): rationale and design overview. Clin J Am Soc Nephrol. 2007 Sep;2(5):898-905.]</ref> | ||
<ref name=" | <ref name="baseline">[http://ndt.oxfordjournals.org/content/27/7/2872.long Chertow GM, et al. Baseline characteristics of subjects enrolled in the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial. Nephrol Dial Transplant. 2012 Jul;27(7):2872-9.]</ref> | ||
</references> | </references> | ||