Prospective Evaluation of an Extended Interval of INR Follow-up in a VA Anticoagulation Service

• Sponsor: William S. Middleton Memorial Veterans Hospital (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT02392104
• Collaborator: University of Wisconsin, Madison (Other)
• Enrollment: 51
• Arm: 1
• Actual Duration (Months): 27

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the feasibility, safety, and acceptability of implementing an extended interval of INR follow-up in Veterans on a stable dose of warfarin in the Anticoagulation Clinic at the William S. Middleton Memorial Veterans Hospital.

All participants will be provided usual care from the anticoagulation clinic, except for the interval between INRs. If the participant continues to be on a stable dose of warfarin and the INRs are within the goal range of 2-3 (including lab variation), follow-up visits will be scheduled following an extended interval protocol. Patient satisfaction will be evaluated at various points throughout the study. Additionally provider satisfaction, confidence, and knowledge of the extended interval protocol will be analyzed. Bleeding and thromboembolic events will be evaluated to ensure the safety of an extended follow-up interval.

Condition or Disease	Intervention/Treatment	Phase
Anticoagulation	Drug: Warfarin	N/A

Detailed Description

The purpose of this study is to determine the feasibility, safety, and acceptability of implementing an extended interval of INR follow-up in Veterans on a stable dose of warfarin in the Anticoagulation Clinic at the William S. Middleton Memorial Veterans Hospital.

All participants will be provided usual care from the anticoagulation clinic, except for the interval between INRs. If the participant continues to be on a stable dose of warfarin and the INRs are within the goal range of 2-3 (including lab variation), follow-up visits will be scheduled following an extended interval protocol, from 5-6 weeks, to 7-8 weeks, to 11-12 weeks and then continued with 11-12 week visits if INRs continue to remain in goal range and appropriate for the patient. Patient satisfaction will be evaluated at baseline, 6-, 12-, and 24-months. Additionally provider satisfaction, confidence, and knowledge of the extended interval protocol will be analyzed. Bleeding and thromboembolic events will be evaluated to ensure the safety of an extended follow-up interval.

Study Design

• Study Type: Interventional
• Actual Enrollment: 51 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prospective Evaluation of an Extended Interval of INR Follow-up in a VA Anticoagulation Service
• Actual Study Start Date: Mar 27, 2015
• Actual Primary Completion Date: Jun 25, 2017
• Actual Study Completion Date: Jun 25, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention Arm All patients in the study will be in the intervention arm.	Drug: Warfarin; If the patient's INRs stay within goal range, their interval of INR follow-up will be extended based on a protocol to a maximum of 12 weeks.; Other Names: Coumadin

Outcome Measures

Primary Outcome Measures

1. Rates of Participant Accrual [up to 2.25 years]

   Number of participants who enroll vs. number of individuals invited

2. Number of Participants Able to be Scheduled for at Least One 12-week Interval [24 months]

   This outcome will determine the number of participants able to be scheduled for at least one 12-week interval

3. Number of Participants Scheduled for at Least 4 Consecutive 12-week Intervals [24 months]

   The outcome will determine the number of participants scheduled for at least 4 consecutive 12-week intervals

Secondary Outcome Measures

1. Change in Frequency of Appointments From Baseline to End of Study [12 and 24 months]

   This outcome will evaluate the change in frequency of appointments from baseline to end of study (at 12 and 24 months)

2. Bleeding and Thromboembolic Events From Baseline [24 months]

   This outcome will determine the number of bleeding and thromboembolic events from baseline

3. Change in Time in Therapeutic Range From Baseline [6, 12, and 24 months]

   The outcome will evaluate the change in time in therapeutic range (TTR) from baseline (intention-to-treat)

4. Patient Satisfaction Through Total DASS Score [baseline, 6 months, 12 months, 24 months]

   Patient satisfaction through total DASS score. DASS = Duke Anticoagulation Satisfaction Scale. 25-item scale.Higher numbers indicate worsening satisfaction ranging from 25-175. Seven-point ordinal scale ("not at all" = 1, "very much" = 7).

Other Outcome Measures

1. Frequency and Type of Protocol Deviations From Both Participants and Study Staff [Up to 2.25 years]

   This outcome determines the frequency and type of protocol deviations from both participants and study staff

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18 years of age or older

• requirement for indefinite warfarin therapy

• target INR of 2-3

• stable weekly warfarin dose for the past 6 months (not more than a single, one-time adjustment (boost/omission) in the past 6 months, planned interruption for a procedure or surgery with INR(s) out of range in the past 6 months would not exclude a patient)

• a patient of the Madison VA anticoagulation clinic for the previous 12 months

Exclusion Criteria:

• consistently drink ≥4 alcoholic beverages/day or a documented episode of alcohol binging in the past 6 months

• diagnosis of cancer and on active chemotherapy/radiotherapy in the past 3 months

• life expectancy of < 1 year

• enrolled in other investigational drug protocols

• only receiving anticoagulation care at the Madison VA for part of the year (e.g. snowbirds)

• receiving visiting nurse services for INR monitoring

• thrombocytopenia (<100K) within past 12 months

• history of bleeding or thromboembolism requiring medical intervention within past 6 months

• treatment for active liver disease (e.g. hepatitis)

• diagnosis or documentation in EMR suggesting cognitive impairment

• activated power of attorney

• inability to provide informed consent

• non-English speaking

• unstable mental health disorder that impairs judgment

• history of non-adherence to anticoagulation clinic policies and procedures (i.e. missed appointments, self-adjustment of warfarin dose, nonadherence, etc.).

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• William S. Middleton Memorial Veterans Hospital
• University of Wisconsin, Madison

Investigators

• Principal Investigator: Carla Staresinic, PharmD, William S. Middleton Memorial Veterans Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 18, 2017

More Information

Publications

None provided.

• Responsible Party: Carla Staresinic, Manager, Anticoagulation Services, William S. Middleton Memorial Veterans Hospital
• ClinicalTrials.gov Identifier: NCT02392104
• Other Study ID Numbers: 2014-1296
• First Posted: Mar 18, 2015
• Last Update Posted: Dec 11, 2019
• Last Verified: Nov 1, 2019

• Keywords provided by Carla Staresinic, Manager, Anticoagulation Services, William S. Middleton Memorial Veterans Hospital: International Normalized Ratio; Warfarin
• Additional relevant MeSH terms: Warfarin

Study Results

Participant Flow

Arm/Group Title	Extended INR Follow-up Interval Group
Arm/Group Description	All patients in the study will be in the intervention arm. Warfarin: If the patient's INRs stay within goal range, their interval of INR follow-up will be extended based on a protocol to a maximum of 12 weeks.
Period Title: Overall Study
STARTED	50
COMPLETED	39
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	Intervention Arm
Arm/Group Description	All patients in the study will be in the intervention arm. Warfarin: If the patient's INRs stay within goal range, their interval of INR follow-up will be extended based on a protocol to a maximum of 12 weeks.
Overall Participants	50
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.4 (7.6)
Sex: Female, Male (Count of Participants)
Female	1 2%
Male	49 98%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	49 98%
More than one race	0 0%
Unknown or Not Reported	1 2%
Region of Enrollment (participants) [Number]
United States	50 100%
HAS-BLED score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	1.8 (0.9)

Outcome Measures

1. Primary Outcome

Title	Rates of Participant Accrual
Description	Number of participants who enroll vs. number of individuals invited
Time Frame	up to 2.25 years

Outcome Measure Data

Analysis Population Description

107 invited to participate in the study, not all enrolled or started the study

Arm/Group Title	Intervention Arm
Arm/Group Description	All patients in the study will be in the intervention arm. Warfarin: If the patient's INRs stay within goal range, their interval of INR follow-up will be extended based on a protocol to a maximum of 12 weeks.
Measure Participants	107
Number of patients invted	107 214%
Patient enrolled in study	51 102%
Patients analyzed for study	50 100%

2. Primary Outcome

Title	Number of Participants Able to be Scheduled for at Least One 12-week Interval
Description	This outcome will determine the number of participants able to be scheduled for at least one 12-week interval
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention Arm
Arm/Group Description	All patients in the study will be in the intervention arm. Warfarin: If the patient's INRs stay within goal range, their interval of INR follow-up will be extended based on a protocol to a maximum of 12 weeks.
Measure Participants	50
Count of Participants [Participants]	36 72%

3. Primary Outcome

Title	Number of Participants Scheduled for at Least 4 Consecutive 12-week Intervals
Description	The outcome will determine the number of participants scheduled for at least 4 consecutive 12-week intervals
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention Arm
Arm/Group Description	All patients in the study will be in the intervention arm. Warfarin: If the patient's INRs stay within goal range, their interval of INR follow-up will be extended based on a protocol to a maximum of 12 weeks.
Measure Participants	50
Count of Participants [Participants]	15 30%

4. Secondary Outcome

Title	Change in Frequency of Appointments From Baseline to End of Study
Description	This outcome will evaluate the change in frequency of appointments from baseline to end of study (at 12 and 24 months)
Time Frame	12 and 24 months

Outcome Measure Data

Analysis Population Description

44 participants remained in the study at 12 months

Arm/Group Title	Intervention Arm
Arm/Group Description	All patients in the study will be in the intervention arm. Warfarin: If the patient's INRs stay within goal range, their interval of INR follow-up will be extended based on a protocol to a maximum of 12 weeks.
Measure Participants	44
Planned anticoagulation visits (baseline)	12.67 (2.56)
Planned anticoagulation visits (0-12 months)	10.43 (3.58)

5. Secondary Outcome

Title	Bleeding and Thromboembolic Events From Baseline
Description	This outcome will determine the number of bleeding and thromboembolic events from baseline
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention Arm
Arm/Group Description	All patients in the study will be in the intervention arm. Warfarin: If the patient's INRs stay within goal range, their interval of INR follow-up will be extended based on a protocol to a maximum of 12 weeks.
Measure Participants	50
Number of thromboembolic events	2
Number of major bleeding events	6
Number of serious bleeding events	16

6. Secondary Outcome

Title	Change in Time in Therapeutic Range From Baseline
Description	The outcome will evaluate the change in time in therapeutic range (TTR) from baseline (intention-to-treat)
Time Frame	6, 12, and 24 months

Outcome Measure Data

Analysis Population Description

49 participants at 12 months, 44 participants at 24 months

Arm/Group Title	Intervention Arm
Arm/Group Description	All patients in the study will be in the intervention arm. Warfarin: If the patient's INRs stay within goal range, their interval of INR follow-up will be extended based on a protocol to a maximum of 12 weeks.
Measure Participants	50
6 months	-12.2 (26.4)
12 months	-7.3 (18.3)
24 months	-4.4 (13.2)

7. Secondary Outcome

Title	Patient Satisfaction Through Total DASS Score
Description	Patient satisfaction through total DASS score. DASS = Duke Anticoagulation Satisfaction Scale. 25-item scale.Higher numbers indicate worsening satisfaction ranging from 25-175. Seven-point ordinal scale ("not at all" = 1, "very much" = 7).
Time Frame	baseline, 6 months, 12 months, 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention Arm
Arm/Group Description	All patients in the study will be in the intervention arm. Warfarin: If the patient's INRs stay within goal range, their interval of INR follow-up will be extended based on a protocol to a maximum of 12 weeks.
Measure Participants	48
baseline	42.89 (12.08)
6 months	43.99 (11.75)
12 months	38.83 (11.53)
24 months	46.82 (15.16)

8. Other Pre-specified Outcome

Title	Frequency and Type of Protocol Deviations From Both Participants and Study Staff
Description	This outcome determines the frequency and type of protocol deviations from both participants and study staff
Time Frame	Up to 2.25 years

Outcome Measure Data

Analysis Population Description

634 eligible participant visits

Arm/Group Title	Intervention Arm
Arm/Group Description	All patients in the study will be in the intervention arm. Warfarin: If the patient's INRs stay within goal range, their interval of INR follow-up will be extended based on a protocol to a maximum of 12 weeks.
Measure Participants	50
Measure participant visits	634
extended interval visits scheduled correctly	94.3
Deviations too short	3.0
Deviations too long	2.7

Adverse Events

Time Frame	24 months
Adverse Event Reporting Description	Major bleeding was defined as a fatal or symptomatic bleed into a critical area or organ, bleeding leading to hospitalization, or transfusion of two units or more of packed red blood cells. This definition is the standard definition used by the Anticoagulation Clinic to report events. Serious bleeding was defined as bleeding leading to emergency or urgent care visit or additional testing required.
Arm/Group Title	Intervention Arm
Arm/Group Description	All patients in the study will be in the intervention arm. Warfarin: If the patient's INRs stay within goal range, their interval of INR follow-up will be extended based on a protocol to a maximum of 12 weeks.
All Cause Mortality
	Intervention Arm
	Affected / at Risk (%)	# Events
Total	0/50 (0%)
Serious Adverse Events
	Intervention Arm
	Affected / at Risk (%)	# Events
Total	15/50 (30%)
Blood and lymphatic system disorders
Multiple myeloma	1/50 (2%)	1
Cardiac disorders
Aortic valve disease	2/50 (4%)	2
Chest pain - cardiac	1/50 (2%)	2
Heart failure	3/50 (6%)	5
Gastrointestinal disorders
Colitis	1/50 (2%)	1
Colonic hemorrhage	1/50 (2%)	1
Hemorrhoidal hemorrhage	1/50 (2%)	1
Hemorrhoids	2/50 (4%)	2
Small intestinal obstruction	1/50 (2%)	1
Upper gastrointestinal hemorrhage	1/50 (2%)	1
Infections and infestations
Bronchial infection	1/50 (2%)	1
Lung infection	1/50 (2%)	1
Musculoskeletal and connective tissue disorders
Arthritis	1/50 (2%)	1
Back pain	1/50 (2%)	1
Renal and urinary disorders
Severe AKI	1/50 (2%)	1
Urinary retention	1/50 (2%)	1
Urinary tract pain	1/50 (2%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension	1/50 (2%)	1
Skin and subcutaneous tissue disorders
RLE cellulitis	1/50 (2%)	1
Vascular disorders
Thromboembolic event	1/50 (2%)	2
Post-op monitoring for vascular procedure	1/50 (2%)	1
Other (Not Including Serious) Adverse Events
	Intervention Arm
	Affected / at Risk (%)	# Events
Total	19/50 (38%)
Blood and lymphatic system disorders
Major bleeding	6/50 (12%)	6
Serious bleeding	16/50 (32%)	22
Vascular disorders
Thromboembolism	1/50 (2%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.