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

NCT ID: NCT03150667

Last Updated: 2018-05-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

220 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-04-10

Study Completion Date

2020-04-30

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Chronic Kidney Diseases Acute Coronary Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Ticagrelor Arm

Eligible patients randomized to the Ticagrelor arm will receive open label drug at a dose selected by their providers along with 81mg aspirin. These patients will be followed for 1 year through chart review for events. For event free patients, a phone follow-up will be done at the end of 1 year to record events These events be documented in the medical records.

Group Type ACTIVE_COMPARATOR

Ticagrelor

Intervention Type DRUG

Ticagrelor in patients with CKD presenting with ACS.

Clopidogrel

Eligible patients randomized to the Clopidogrel arm will receive open label drug at a dose selected by their providers along with 81mg aspirin. These patients will be followed for 1 year through chart review for events. For event free patients, a phone follow-up will be done at the end of 1 year to record events These events be documented in the medical records

Group Type ACTIVE_COMPARATOR

Clopidogrel

Intervention Type DRUG

Clopidogrel in patients with CKD presenting with ACS.

Interventions

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Ticagrelor

Ticagrelor in patients with CKD presenting with ACS.

Intervention Type DRUG

Clopidogrel

Clopidogrel in patients with CKD presenting with ACS.

Intervention Type DRUG

Other Intervention Names

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Brilinta Plavix

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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North Texas Veterans Healthcare System

FED

Sponsor Role lead

Responsible Party

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Subhash Banerjee

Chief, Division of Cardiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Durham VA Medical Center

Durham, North Carolina, United States

Site Status RECRUITING

VA North Texas Health Care System

Dallas, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Subhash Banerjee, MD

Role: CONTACT

214-867-1608

Amutharani Baskar, MBBS

Role: CONTACT

214-857-0305

Facility Contacts

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Sunil Rao, MD

Role: primary

919-286-0411

Marc Samsky, MD

Role: backup

Subhash Banerjee, MD

Role: primary

214-857-1608

Amutharani Baskar, MBBS

Role: backup

214-857-0305

References

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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. doi: 10.1016/s0735-1097(02)01745-x.

Reference Type BACKGROUND
PMID: 11923033 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18371477 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18721508 (View on PubMed)

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. doi: 10.1038/sj.ki.5001934. Epub 2006 Oct 18.

Reference Type BACKGROUND
PMID: 17051142 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19427428 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20065168 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18450830 (View on PubMed)

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. doi: 10.1001/jama.293.17.2126.

Reference Type BACKGROUND
PMID: 15870416 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24662983 (View on PubMed)

Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.

Reference Type DERIVED
PMID: 35224730 (View on PubMed)

Other Identifiers

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16-041

Identifier Type: -

Identifier Source: org_study_id

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