Study Comparing Treatment Effectiveness of Guideline Indicated APT for ACS in Patients With CKD

Acute Coronary Syndrome Clinical Trial

— CPRS-CKD  

Official title:

Pragmatic Randomized Controlled Trial Comparing Treatment Effectiveness of Guideline Indicated Anti-platelet Therapy for Acute Coronary Syndrome in Patients With Chronic Kidney Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03150667
• Other study ID #: 16-041
• Status: Recruiting
• Phase: Phase 4
• Start date: April 10, 2017
• Est. completion date: April 30, 2020

Study information

• Verified date: May 2018
• Source: North Texas Veterans Healthcare System
• Contact: Subhash Banerjee, MD
• Phone: 214-867-1608
• Email: subhash.banerjee[@]utsouthwestern.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To compare clinical outcomes in patients with chronic kidney disease (CKD) presenting with an acute coronary syndrome (ACS) treated with clopidogrel or ticagrelor (both FDA approved and guideline indicated drugs for treating these patients upstream managed medically or with coronary revascularization).

Description:

The purpose of this trial is to see if ticagrelor is a better antiplatelet treatment option than clopidogrel for dual antiplatelet therapy (with aspirin) in chronic kidney disease (CKD) patients presenting with acute coronary syndrome (ACS). This study will be a comparative effectiveness trial of the two guideline-based treatments for patients with ACS with CKD, who are at a significantly higher risk of mortality and morbidity and often receive sub-optimal treatment. Ticagrelor and clopidogrel are the only two drugs in ACS that are approved for upstream (on admission) use both in CKD and non-CKD patients who are managed both medically (conservatively) or with coronary revascularization (with PCI-percutaneous coronary revascularization or CABG-coronary artery bypass graft surgery). Both of these drugs are not cleared renally and do not require dose adjustments in any stage of CKD.

Moreover, as a significant majority of CKD patients presenting with ACS are initially cared for by internists, hospitalists, and nephrologists, execution of this study at VA hospitals will strengthen collaboration between these specialties with cardiology and help adopt best practice pathways across multiple services participating in the care of this high-risk patient population. Finally, the study and its findings will for the first time provide randomized clinical trial evidence to guide the care of CKD patients with ACS who are at a high risk for both recurrent ischemia and bleeding complications.

Hypothesis to be tested: The Investigators hypothesize that use of guideline-indicated dual antiplatelet therapy (DAPT) with ticagrelor compared to clopidogrel in CKD patients presenting with ACS will reduce ischemic cardiovascular events at 1 year, additionally without a significant increase in severe bleeding (Bleeding Associated Research Consortium or BARC >3 category) over the same period. This hypothesis is based on prior subgroup analysis of published studies.

Randomized patients will be followed for 1 year from date of admission and events recorded through chart review. For patients who are event free, a phone follow-up will be done at the end of 1 year to note events, which will be recorded on the medical chart as well.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: April 30, 2020
• Est. primary completion date: April 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Hospital admission with non-emergent ACS qualifying diagnosis: chest pain, unstable angina or NSTEMI

• A decision to prescribe clopidogrel or ticagrelor in addition to aspirin (DAPT-dual antiplatelet therapy) by the attending physician

• A eGFR< 60 mL/min per 1.73 m.2 (as defined in the EMR or CPRS reported results)

Exclusion Criteria:

• Diagnosis of ST Elevation Myocardial Infarction (STEMI) at admission

• History of intra-cranial hemorrhage

• Bleeding requiring hospitalization, surgery, or transfusion within the past 3 months

• Life expectancy in the opinion of the provider < 6 months

• Chronic antithrombotic therapy

• Known allergy to clopidogrel or ticagrelor

• Patients on hemodialysis

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Chronic Kidney Diseases
• Kidney Diseases
• Renal Insufficiency, Chronic
• Syndrome

Intervention

Drug:
• Ticagrelor
Ticagrelor in patients with CKD presenting with ACS.
• Clopidogrel
Clopidogrel in patients with CKD presenting with ACS.

Locations

Country	Name	City	State
United States	VA North Texas Health Care System	Dallas	Texas
United States	Durham VA Medical Center	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
North Texas Veterans Healthcare System

Country where clinical trial is conducted

United States, 

References & Publications (9)

Best PJ, Lennon R, Ting HH, Bell MR, Rihal CS, Holmes DR, Berger PB. The impact of renal insufficiency on clinical outcomes in patients undergoing percutaneous coronary interventions. J Am Coll Cardiol. 2002 Apr 3;39(7):1113-9. — View Citation

Best PJ, Steinhubl SR, Berger PB, Dasgupta A, Brennan DM, Szczech LA, Califf RM, Topol EJ; CREDO Investigators. The efficacy and safety of short- and long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease: results from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial. Am Heart J. 2008 Apr;155(4):687-93. doi: 10.1016/j.ahj.2007.10.046. Epub 2008 Feb 21. — View Citation

Bonello L, De Labriolle A, Roy P, Steinberg DH, Okabe T, Pinto Slottow TL, Xue Z, Torguson R, Suddath WO, Satler LF, Kent KM, Pichard AD, Lindsay J, Waksman R. Impact of optimal medical therapy and revascularization on outcome of patients with chronic kidney disease and on dialysis who presented with acute coronary syndrome. Am J Cardiol. 2008 Sep 1;102(5):535-40. doi: 10.1016/j.amjcard.2008.04.040. Epub 2008 Jun 26. — View Citation

Charytan D, Kuntz RE. The exclusion of patients with chronic kidney disease from clinical trials in coronary artery disease. Kidney Int. 2006 Dec;70(11):2021-30. Epub 2006 Oct 18. — View Citation

Dasgupta A, Steinhubl SR, Bhatt DL, Berger PB, Shao M, Mak KH, Fox KA, Montalescot G, Weber MA, Haffner SM, Dimas AP, Steg PG, Topol EJ; CHARISMA Investigators. Clinical outcomes of patients with diabetic nephropathy randomized to clopidogrel plus aspirin versus aspirin alone (a post hoc analysis of the clopidogrel for high atherothrombotic risk and ischemic stabilization, management, and avoidance [CHARISMA] trial). Am J Cardiol. 2009 May 15;103(10):1359-63. doi: 10.1016/j.amjcard.2009.01.342. Epub 2009 Apr 1. — View Citation

Fox CS, Muntner P, Chen AY, Alexander KP, Roe MT, Cannon CP, Saucedo JF, Kontos MC, Wiviott SD; Acute Coronary Treatment and Intervention Outcomes Network registry. Use of evidence-based therapies in short-term outcomes of ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction in patients with chronic kidney disease: a report from the National Cardiovascular Data Acute Coronary Treatment and Intervention Outcomes Network registry. Circulation. 2010 Jan 26;121(3):357-65. doi: 10.1161/CIRCULATIONAHA.109.865352. Epub 2010 Jan 11. — View Citation

Hwang SJ, Lin MY, Chen HC, Hwang SC, Yang WC, Hsu CC, Chiu HC, Mau LW. Increased risk of mortality in the elderly population with late-stage chronic kidney disease: a cohort study in Taiwan. Nephrol Dial Transplant. 2008 Oct;23(10):3192-8. doi: 10.1093/ndt/gfn222. Epub 2008 May 1. — View Citation

Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G, Airoldi F, Chieffo A, Montorfano M, Carlino M, Michev I, Corvaja N, Briguori C, Gerckens U, Grube E, Colombo A. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA. 2005 May 4;293(17):2126-30. — View Citation

James MT, Pannu N. Early-invasive strategies for the management of coronary heart disease in chronic kidney disease: is acute kidney injury a consideration? Curr Opin Nephrol Hypertens. 2014 May;23(3):283-90. doi: 10.1097/01.mnh.0000444819.03121.4b. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of all-cause mortality, non-fatal myocardial infarction (MI), or ischemic stroke	Occurrence of all-cause mortality, non-fatal myocardial infarction (MI), or ischemic stroke	1 year from date of admission
Secondary	Occurrence of bleeding	Incidence of BARC >3 bleeding over a period of 1-year from hospital admission	1 year from date of admission
Secondary	Need for ischemia driven urgent coronary revascularization	Need for ischemia driven urgent coronary revascularization (UCR) over a period of 1-year from hospital admission	1 year from date of admission
Secondary	Occurrence of MACE events	Comparison of 12-month post-randomization MACE events, a composite of all-cause death, MI, ischemic stroke, or UCR in participant groups	1 year from date of admission
Secondary	Length of hospital stay and readmission	Post-PCI length of hospital stay and readmission = 1 year of initial discharge	1 year from date of admission