Prevention of Stroke and Systemic Embolic Events in Patients With Atrial Fibrillation

NCT00684307 | Completed Phase 2 Results DMC

• 1 other identifier: D1250C00008
• Study Type: interventional
• Target: 1,084
• Locations: 0 countries
• Sites: N/A

Brief Summary

The main purpose of this study is to provide dose-guiding information by assessing the safety and tolerability of 4 different dosing regimens of an extended-release (ER) formulation of AZD0837 compared with well-controlled, dose-adjusted Vitamin-K antagonists (VKA) (aiming for an international normalized ratio (INR) 2.0 to 3.0) in patients with non-valvular atrial fibrillation (AF) with one or more additional risk factors for stroke.

Conditions

Nonvalvular Atrial Fibrillation

Keywords

Anticoagulant Treatment; Risk Factors For Stroke

Outcome Measures

Primary Outcomes (4)

• Bleeding Events

  Number of patients with a bleeding event while on study drug. Patients with multiple events are counted once

  36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)

• Creatinine

  Change in Creatinine values from baseline to week 12 visit for patients while on study drug (week 12 visit-baseline)

  12 weeks according to protocol.(baseline to week 12 visit)

• Alanine Aminotransferase (ALAT)

  Number of patients while on study drug with ALAT\>=3 times upper limit of normal.l

  36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)

• Bilirubin

  Number of patients while on study drug with Bilirubin\>=2 times upper limit of normal

  36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)

Secondary Outcomes (8)

• D-Dimer

  14 weeks according to protocol.(enrolment to week 12 visit)

• Activated Partial Thromboplastin Time (APTT)

  12 weeks according to protocol.(baseline to week 12 visit)

• Ecarin Clotting Time (ECT)

  12 weeks according to protocol.(baseline to week 12 visit)

• Plasma Concentration of AZD0837 (Prodrug)

  12 weeks after baseline according to protocol

• Plasma Concentration of AR-H067637XX (Active Metabolite)

  12 weeks after baseline according to protocol

Study Arms (5)

1

EXPERIMENTAL

AZD0837 450 mg

Drug: AZD0837

2

EXPERIMENTAL

AZD0837 200 mg

Drug: AZD0837

3

EXPERIMENTAL

AZD0837 300 mg

Drug: AZD0837

4

EXPERIMENTAL

AZD0837 150 mg

Drug: AZD0837

5

ACTIVE COMPARATOR

Vitamin-K antagonist at INR 2-3

Drug: Vitamin-K antagonist at INR 2-3

Interventions

AZD0837 DRUG

ER tablet, PO, once daily for a period of 3-9 months.

1; 3; 4

Vitamin-K antagonist at INR 2-3 DRUG

Tablet, PO for a period of 3-9 months.

Also known as: Warfarin

5

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Nonvalvular AF (NVAF) verified by at least two ECGs in the last year separated by at least one week.
• Previous cerebral ischemic attack (stroke or TIA, \>30 days prior to randomization)
• Previous systemic embolism.
• Symptomatic congestive heart failure (CHF)
• Impaired left ventricular systolic function
• Diabetes mellitus
• Hypertension requiring anti-hypertensive treatment.

You may not qualify if:

• AF secondary to reversible disorders, eg hyperthyroidism, drugs and pulmonary embolism
• Known contraindication to VKA treatment
• Presence of a valvular heart disease, mechanical heart valves, active endocarditis, left ventricular aneurysm or thrombus, atrial myxoma or any condition other than AF requiring chronic anticoagulation treatment
• Conditions associated with increased risk of major bleeding for example: history of intracranial bleeding, history of bleeding gastrointestinal disorder or major surgical procedure or trauma two weeks prior to randomization

Sponsors & Collaborators

• AstraZeneca: lead

Related Publications (1)

• Lip GY, Rasmussen LH, Olsson SB, Jensen EC, Persson AL, Eriksson U, Wahlander KF; Steering Committee. Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: a randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs. vitamin K antagonists. Eur Heart J. 2009 Dec;30(23):2897-907. doi: 10.1093/eurheartj/ehp318. Epub 2009 Aug 18.

  PMID: 19690349 DERIVED

MeSH Terms

Interventions

AZD 0837; Warfarin

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Gerard Lynch
• Organization: AstraZeneca

aztrial_results_posting@astrazeneca.com

Study Officials

• Gregory Y Lip, Prof

  University Department of Medicine, City Hospital, Birmingham, B18 7QH, England, UK

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2008
• First Posted: May 26, 2008
• Study Start: February 1, 2007
• Primary Completion: June 1, 2008
• Study Completion: June 1, 2008
• Last Updated: March 23, 2012
• Results First Posted: September 22, 2011

Record last verified: 2012-03