ATIVO: Anticoagulation Therapy in the Very Old

• Sponsor: Robert Stein (Other)
• Overall Status: Completed
• CT.gov ID: NCT03103763
• Collaborator: (none)
• Enrollment: 132
• Location: 1
• Actual Duration (Months): 29.5
• Patients Per Site Per Month: 4.5

Study Details

Study Description

Brief Summary

This study is designed to evaluate the efficacy and safety of warfarin anticoagulation in the very old and attempt to identify risk factors which may impede safe and effective anticoagulation.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation	Drug: Warfarin

Detailed Description

This is a prospective registry study with data being collected continuously for 24 months.

Patients who have electrocardiographically confirmed atrial fibrillation, are being followed by the Pen Bay Medical Center Anticoagulation Services and are at least 90 years old will be recruited into the study. A matched cohort of patients between the ages of 80 and 89 and another matched cohort of patients between the ages of 70 and 79 will also be recruited into the study for comparison.

Data related to adverse events, concomitant medications, living arrangements, mobility and alcohol use will be collected every 6 months. In addition the CHA2DS2-VASc (score for atrial fibrillation stroke risk), HAS - BLED (major bleeding risk score for patients on anticoagulation), frailty and Mini Cog scores will be recalculated at each visit.

Study Design

• Study Type: Observational
• Actual Enrollment: 132 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: ATIVO Study - Anticoagulation Therapy in the Very Old
• Actual Study Start Date: Mar 20, 2017
• Actual Primary Completion Date: Sep 3, 2019
• Actual Study Completion Date: Sep 3, 2019

Arms and Interventions

Arm	Intervention/Treatment
Aged 90 and older Subjects 90 years and older with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services.	Drug: Warfarin; Patients on warfarin for atrial fibrillation; Other Names: Coumadin, Jantoven
Aged 80-89 Subjects aged 80-89 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services.	Drug: Warfarin; Patients on warfarin for atrial fibrillation; Other Names: Coumadin, Jantoven
Aged 70-79 Subjects aged 70-79 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services.	Drug: Warfarin; Patients on warfarin for atrial fibrillation; Other Names: Coumadin, Jantoven

Outcome Measures

Primary Outcome Measures

1. Number of Patients Experiencing Stroke [24 months]

   Every 6 months the medical record was reviewed for evidence of stroke of any cause.

2. Number of Patients Experiencing a Major Bleeding Event [24 months]

   defined as one of the following: fatal bleeding, symptomatic bleeding in a critical area or organ or bleeding causing a fall in hemoglobin of 2 g/dl or more or leading to a transfusion of 2 or more units of whole blood or red cells

Secondary Outcome Measures

1. Number of Patients Experiencing a Traumatic Subdural Hemorrhage [24 months]

   Number of subjects who experienced a traumatic subdural hemorrhage in each age group

2. Number of Patients Experiencing a Traumatic Intracerebral Hemorrhage [24 months]

   Number of subjects who experienced a traumatic intracerebral hemorrhage in each age group

3. Number of Hospitalizations Patients Experienced [24 months]

   Every 6 months the medical record was reviewed for any hospitalizations experienced by the subject within our healthcare system.

4. Number of Patients Experiencing Cardiovascular Death [24 months]

   Every 6 months the medical record was reviewed. All deaths were researched for cause and noted if the cause was related to the cardiovascular system.

5. Number of Patients Experiencing Death Related to Anticoagulation [24 months]

   All deaths were reviewed in the medical record to determine the cause and if it was related in any way to the use of anticoagulation therapy.

6. Mean Time in Therapeutic Range at End of Study Participation [up to 24 months]

   International Normalized Ratio (INR) time in therapeutic range at the end of the individual's study participation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 70 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 70 years of age or older

• electrocardiographically confirmed atrial fibrillation

• anticipated regular follow up with patient by Penobscot Bay Medical Center (PBMC) Anticoagulation Services

• Subject or legally authorized representative must be willing to provide informed consent

Exclusion Criteria:

• Patients not being followed by the PBMC Anticoagulation Services

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Penobscot Bay Medical Center	Rockport	Maine	United States	04856

Sponsors and Collaborators

• Robert Stein

Investigators

• Principal Investigator: Robert W. Stein, MD, MaineHealth

Study Documents (Full-Text)

• Study Protocol - Dec 13, 2018
• Statistical Analysis Plan - Mar 13, 2020
• Informed Consent Form - Mar 20, 2017

More Information

Publications

None provided.

• Responsible Party: Robert Stein, Medical Director of Anticoagulation Services, MaineHealth
• ClinicalTrials.gov Identifier: NCT03103763
• Other Study ID Numbers: PenobscotBMC
• First Posted: Apr 6, 2017
• Last Update Posted: Aug 17, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Robert Stein, Medical Director of Anticoagulation Services, MaineHealth: Elderly; Anticoagulation; Risk Assessment
• Additional relevant MeSH terms: Atrial Fibrillation; Warfarin

Study Results

Participant Flow

Arm/Group Title	Aged 90 and Older	Aged 80-89	Aged 70-79
Arm/Group Description	Subjects 90 years and older with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 80-89 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 70-79 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation
Period Title: Overall Study
STARTED	44	44	44
COMPLETED	29	36	37
NOT COMPLETED	15	8	7

Baseline Characteristics

Arm/Group Title	Aged 90 and Older	Aged 80-89	Aged 70-79	Total
Arm/Group Description	Subjects 90 years and older with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 80-89 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 70-79 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Total of all reporting groups
Overall Participants	44	44	44	132
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%
>=65 years	44 100%	44 100%	44 100%	132 100%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	93	84	74	84
Sex: Female, Male (Count of Participants)
Female	31 70.5%	25 56.8%	23 52.3%	79 59.8%
Male	13 29.5%	19 43.2%	21 47.7%	53 40.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	44 100%	44 100%	44 100%	132 100%
Region of Enrollment (participants) [Number]
United States	44 100%	44 100%	44 100%	132 100%
Living at home alone (Count of Participants)
Count of Participants [Participants]	11 25%	18 40.9%	9 20.5%	38 28.8%
Living at home with paid help (Count of Participants)
Count of Participants [Participants]	2 4.5%	2 4.5%	1 2.3%	5 3.8%
Living at home with family (Count of Participants)
Count of Participants [Participants]	27 61.4%	24 54.5%	34 77.3%	85 64.4%
Living in assisted living (Count of Participants)
Count of Participants [Participants]	4 9.1%	0 0%	0 0%	4 3%
Living in Long Term Care (Count of Participants)
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Experiencing Stroke
Description	Every 6 months the medical record was reviewed for evidence of stroke of any cause.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Three subjects in the 80-89 age group and two subjects in the 70-79 age group withdrew consent prior to end of study.

Arm/Group Title	Aged 90 and Older	Aged 80-89	Aged 70-79
Arm/Group Description	Subjects 90 years and older with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 80-89 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 70-79 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation
Measure Participants	44	41	42
Count of Participants [Participants]	2 4.5%	2 4.5%	0 0%

2. Primary Outcome

Title	Number of Patients Experiencing a Major Bleeding Event
Description	defined as one of the following: fatal bleeding, symptomatic bleeding in a critical area or organ or bleeding causing a fall in hemoglobin of 2 g/dl or more or leading to a transfusion of 2 or more units of whole blood or red cells
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Three subjects in the 80-89 age group and two subjects in the 70-79 age group withdrew consent prior to end of study.

Arm/Group Title	Aged 90 and Older	Aged 80-89	Aged 70-79
Arm/Group Description	Subjects 90 years and older with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 80-89 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 70-79 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation
Measure Participants	44	41	42
Count of Participants [Participants]	4 9.1%	2 4.5%	4 9.1%

3. Secondary Outcome

Title	Number of Patients Experiencing a Traumatic Subdural Hemorrhage
Description	Number of subjects who experienced a traumatic subdural hemorrhage in each age group
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Three subjects in the 80-89 age group and two subjects in the 70-79 age group withdrew consent prior to end of study.

Arm/Group Title	Aged 90 and Older	Aged 80-89	Aged 70-79
Arm/Group Description	Subjects 90 years and older with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 80-89 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 70-79 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation
Measure Participants	44	41	42
Count of Participants [Participants]	0 0%	0 0%	0 0%

4. Secondary Outcome

Title	Number of Patients Experiencing a Traumatic Intracerebral Hemorrhage
Description	Number of subjects who experienced a traumatic intracerebral hemorrhage in each age group
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Three subjects in the 80-89 age group and two subjects in the 70-79 age group withdrew consent prior to end of study.

Arm/Group Title	Aged 90 and Older	Aged 80-89	Aged 70-79
Arm/Group Description	Subjects 90 years and older with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 80-89 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 70-79 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation
Measure Participants	44	41	42
Count of Participants [Participants]	0 0%	0 0%	0 0%

5. Secondary Outcome

Title	Number of Hospitalizations Patients Experienced
Description	Every 6 months the medical record was reviewed for any hospitalizations experienced by the subject within our healthcare system.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Three subjects in the 80-89 age group and two subjects in the 70-79 age group withdrew consent prior to end of study.

Arm/Group Title	Aged 90 and Older	Aged 80-89	Aged 70-79
Arm/Group Description	Subjects 90 years and older with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 80-89 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 70-79 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation
Measure Participants	44	41	42
Number [hospitalizations]	51	41	41

6. Secondary Outcome

Title	Number of Patients Experiencing Cardiovascular Death
Description	Every 6 months the medical record was reviewed. All deaths were researched for cause and noted if the cause was related to the cardiovascular system.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Three subjects in the 80-89 age group and two subjects in the 70-79 age group withdrew consent prior to end of study.

Arm/Group Title	Aged 90 and Older	Aged 80-89	Aged 70-79
Arm/Group Description	Subjects 90 years and older with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 80-89 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 70-79 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation
Measure Participants	44	41	42
Count of Participants [Participants]	15 34.1%	5 11.4%	5 11.4%

7. Secondary Outcome

Title	Number of Patients Experiencing Death Related to Anticoagulation
Description	All deaths were reviewed in the medical record to determine the cause and if it was related in any way to the use of anticoagulation therapy.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Three subjects in the 80-89 age group and two subjects in the 70-79 age group withdrew consent prior to end of study.

Arm/Group Title	Aged 90 and Older	Aged 80-89	Aged 70-79
Arm/Group Description	Subjects 90 years and older with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 80-89 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 70-79 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation
Measure Participants	44	41	42
Count of Participants [Participants]	0 0%	0 0%	0 0%

8. Secondary Outcome

Title	Mean Time in Therapeutic Range at End of Study Participation
Description	International Normalized Ratio (INR) time in therapeutic range at the end of the individual's study participation.
Time Frame	up to 24 months

Outcome Measure Data

Analysis Population Description

All subjects were included in this analysis.

Arm/Group Title	Aged 90 and Older	Aged 80-89	Aged 70-79
Arm/Group Description	Subjects 90 years and older with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 80-89 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation	Subjects aged 70-79 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation
Measure Participants	44	44	44
Mean (Standard Deviation) [percent of time in therapeutic range]	72 (17)	76 (18)	70 (17)

Adverse Events

Time Frame	Because the study is a registry, no events were collected as adverse events. Outcomes were collected. All cause mortality was collected from date of consent up to 24 months.
Adverse Event Reporting Description	Death information was available. However, serious and other adverse event data were not monitored.
Arm/Group Title	Aged 90 and Older		Aged 80-89		Aged 70-79
Arm/Group Description	Subjects 90 years and older with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation		Subjects aged 80-89 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation		Subjects aged 70-79 with atrial fibrillation, taking warfarin, followed by the Penobscot Bay Medical Center Anticoagulation Services. Warfarin: Patients on warfarin for atrial fibrillation
All Cause Mortality
	Aged 90 and Older		Aged 80-89		Aged 70-79
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/44 (34.1%)		5/41 (12.2%)		5/42 (11.9%)
Serious Adverse Events
	Aged 90 and Older		Aged 80-89		Aged 70-79
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Aged 90 and Older		Aged 80-89		Aged 70-79
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

The small sample size limits the power of this study.

More Information

Certain Agreements

Principal Investigators are NOT 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.