The Home INR Study (THINRS)

CSP #481 - The Home INR Study (THINRS)

Since home monitors of prothrombin time (PT) may potentially improve the safety, quality, and convenience of chronic anticoagulation management, it is likely that there will be demands from providers, patients, and manufacturers to make home monitors available to VA patients. The rationale for patient self-testing (PST) is that, compared to conventional high quality anticoagulation management (HQACM), it would permit more intense monitoring and increased patient participation in his/her own care, resulting in increased precision in anticoagulation control and thus fewer events of thromboembolism (strokes) and bleeding. The secondary hypothesis is that PST and HQACM will be comparable in terms of health care utilization and cost.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Procedure: Weekly patient self-testing of prothrombin time; Other: High quality anticoagulation management (HQACM) with conventional monthly testing

Detailed Description

Intervention: Weekly patient self-testing (PST) of prothrombin time by international normalized ratio (PT INR) versus conventional monthly high quality anticoagulation management (HQACM) from an anticoagulation clinic with a minimum two years follow-up.

Primary Hypothesis: Compared to conventional monitoring in the clinic, PST of anticoagulation intensity will decrease the number of events of thromboembolism (strokes), bleeding, and all cause deaths and improve the quality of anticoagulation.

Second Hypothesis: PST and conventional monitoring will be comparable in terms of health care utilization and cost.

Primary Outcomes: Event rates (thromboembolism or bleeding episodes), time to first event, time within therapeutic range for anticoagulation intensity, and total health care cost (including price of PST monitors) and utilization.

Study Abstract: Since home monitors of prothrombin time (PT) may potentially improve the safety, quality, and convenience of chronic anticoagulation management, it is likely that there will be demands from providers, patients, and manufacturers to make home monitors available to VA patients. The rationale for PST is that it would permit more intense monitoring and increased patient participation in his/her own care, resulting in increased precision in anticoagulation control and thus fewer events.

Original plan was for a study at 32 sites with a total sample size of about 3,200 patients and a length of three years (one for recruitment and two years of follow-up). Final status was 28 sites that randomized 2922 patients in 2.75 years of recruitment with a minimum of two years of follow-up.

• Study Type: Interventional
• Enrollment (Actual): 2922
• Phase: Phase 4

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00921
    • VA Medical Center, San Juan
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • VA Medical Center, Birmingham
  • California
    • Fresno, California, United States, 93703
      • VA Central California Health Care System, Fresno
    • Loma Linda, California, United States, 92357
      • VA Medical Center, Loma Linda
    • Palo Alto, California, United States, 94304-1290
      • VA Palo Alto Health Care System
    • West Los Angeles, California, United States, 90073
      • VA Greater Los Angeles Healthcare System, West LA
  • Colorado
    • Denver, Colorado, United States, 80220
      • VA Eastern Colorado Health Care System, Denver
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • VA Connecticut Health Care System (West Haven)
  • Illinois
    • Hines, Illinois, United States, 60141-5000
      • Edward Hines, Jr. VA Hospital
    • North Chicago, Illinois, United States, 60064
      • VA Medical Center, North Chicago
  • Iowa
    • Iowa City, Iowa, United States, 52246-2208
      • VA Medical Center, Iowa City
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • VA Maryland Health Care System, Baltimore
  • Michigan
    • Detroit, Michigan, United States, 48201
      • John D. Dingell VA Medical Center, Detroit
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • VA Medical Center, Minneapolis
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • VA Medical Center, Kansas City MO
  • Nevada
    • North Las Vegas, Nevada, United States, 89036
      • Las Vegas
    • Reno, Nevada, United States, 89502
      • VA Sierra Nevada Health Care System
  • New York
    • Bronx, New York, United States, 10468
      • VA Medical Center, Bronx
    • Buffalo, New York, United States, 14215
      • VA Western New York Healthcare System at Buffalo
    • Syracuse, New York, United States, 13210
      • VA Medical Center, Syracuse
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Durham VA Medical Center HSR&D COE
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • VA Medical Center, Cleveland
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • VA Medical Center, Oklahoma City
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15240
      • VA Pittsburgh Health Care System
  • Rhode Island
    • Providence, Rhode Island, United States, 02908
      • VA Medical Center, Providence
  • Texas
    • Dallas, Texas, United States, 75216
      • VA North Texas Health Care System, Dallas
    • San Antonio, Texas, United States, 78229
      • VA South Texas Health Care System, San Antonio
  • Virginia
    • Salem, Virginia, United States, 24153
      • VA Medical Center, Salem VA
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Wlliam S. Middleton Memorial Veterans Hospital, Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

To be enrolled in this study, patients must:

1. have AF and/or a MHV;
2. be scheduled to receive warfarin indefinitely (operationally defined as 2 years);
3. be using warfarin according to the criteria described in the Coumadin package insert (no off-label uses);
4. be expected to survive for the duration of the study;
5. not be suffering from intracranial bleeding (intracranial hemorrhage, subarachnoid hemorrhage, hemorrhagic stroke) or any other contraindication described in the Coumadin package insert;
6. be willing to perform PST;
7. be willing to be randomized;
8. possess adequate cognitive and language skills to follow the protocol and all related instructions;
9. be willing to participate for the full duration of the study;
10. sign the informed consent form; and
11. not be enrolled in another randomized clinical trial that involves a drug or device intervention.

Exclusion Criteria:

Patients are excluded in this study if:

1. subject has had intracranial hemorrhage, subarachnoid hemorrhage, hemorrhagic stroke, or any other absolute/major contraindication described in the warfarin package insert within the last month
2. subject enrolled in another randomized clinical trial that involves a drug or device intervention
3. subject is not able to follow the protocol and all related instructions, and does not have a caregiver with these skills

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1; Patient Self-Testing (PST) of prothrombin time by international normalized ratio (PT-INR or INR) with weekly testing	Procedure: Weekly patient self-testing of prothrombin time
Other: Arm 2; High quality anticoagulation management (HQACM) with conventional monthly testing	Other: High quality anticoagulation management (HQACM) with conventional monthly testing; HQACM with testing every 4 weeks and as indicated for out of range values, medication/clinical changes.; Other Names: HQACM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Event (Death, Stroke, Major Bleed)	Time to first event (death, stroke, major bleed) The primary outcome was time to first event, and we used the Kaplan-Meier method to compare survival curves and the results using the log-rank test. The number of patients with a primary outcome is what was reported in the NEJM paper. Below is the unpublished cumulative incidence information.	Time to event

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in Therapeutic Range Over Full Length of Follow-up (0 to 100 Percent)	Time in target range (TTR) based on Prothrombin Time standardized to the International Normalized Ratio	Full length of follow-up; average of 3 years
DASS at 2 Years of Follow-up	Satisfaction with care was quantified using the Duke Anticoagulation Satisfaction Scale (DASS). Scores range from 25 to 225, with lower scores indicating higher satisfaction.	At two years of follow-up
Cumulative Gain in Health Utilities at 2 Year	Scores range from -0.36 to 1.00 per year, with a negative score indicating a state worse than being dead and a score of 1.00 indicating perfect health. Since the time frame is 2 years, the range is -0.72 to 2.00.	After 2 years of follow-up for each subject
Health Care Costs at 2 Year		After 2 years of follow-up for each subject

Collaborators and Investigators

• Sponsor: US Department of Veterans Affairs
• Investigators: Study Chair: David B. Matchar, MD, Durham VA Medical Center HSR&D COE

Publications and helpful links

General Publications

• Dolor RJ, Ruybalid RL, Uyeda L, Edson RG, Phibbs C, Vertrees JE, Shih MC, Jacobson AK, Matchar DB; THINRS Site Investigators. An evaluation of patient self-testing competency of prothrombin time for managing anticoagulation: pre-randomization results of VA Cooperative Study #481--The Home INR Study (THINRS). J Thromb Thrombolysis. 2010 Oct;30(3):263-75. doi: 10.1007/s11239-010-0499-8.
• Matchar DB, Jacobson A, Dolor R, Edson R, Uyeda L, Phibbs CS, Vertrees JE, Shih MC, Holodniy M, Lavori P; THINRS Executive Committee and Site Investigators. Effect of home testing of international normalized ratio on clinical events. N Engl J Med. 2010 Oct 21;363(17):1608-20. doi: 10.1056/NEJMoa1002617. Erratum In: N Engl J Med. 2011 Jan 6;364(1):93.
• Matchar DB, Jacobson AK, Edson RG, Lavori PW, Ansell JE, Ezekowitz MD, Rickles F, Fiore L, Boardman K, Phibbs C, Fihn SD, Vertrees JE, Dolor R. The impact of patient self-testing of prothrombin time for managing anticoagulation: rationale and design of VA Cooperative Study #481--the Home INR Study (THINRS). J Thromb Thrombolysis. 2005 Jun;19(3):163-72. doi: 10.1007/s11239-005-1452-0.
• Phibbs CS, Love SR, Jacobson AK, Edson R, Su P, Uyeda L, Matchar DB; writing for the THINRS Executive Committee and Site Investigators. At-Home Versus In-Clinic INR Monitoring: A Cost-Utility Analysis from The Home INR Study (THINRS). J Gen Intern Med. 2016 Sep;31(9):1061-7. doi: 10.1007/s11606-016-3700-8. Epub 2016 May 27.
• Matchar DB, Love SR, Jacobson AK, Edson R, Uyeda L, Phibbs CS, Dolor RJ. The impact of frequency of patient self-testing of prothrombin time on time in target range within VA Cooperative Study #481: The Home INR Study (THINRS), a randomized, controlled trial. J Thromb Thrombolysis. 2015 Jul;40(1):17-25. doi: 10.1007/s11239-014-1128-8.

Study record dates

Study Major Dates

• Study Start: August 1, 2003
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: March 27, 2002
• First Submitted That Met QC Criteria: March 27, 2002
• First Posted (Estimate): March 28, 2002

Study Record Updates

• Last Update Posted (Estimate): April 15, 2014
• Last Update Submitted That Met QC Criteria: March 18, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: AF; Mechanical heart valve (MHV)
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Hemostatics; Coagulants; Thrombin
• Other Study ID Numbers: 481

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No