Anticoagulation After GI Bleeding Pilot Study and Registry (PANTHER-GI)
Primary Purpose
GastroIntestinal Bleeding, Anticoagulant-induced Bleeding
Status
Not yet recruiting
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Restart DOAC within 7 days of clinical hemostasis after GI bleeding
Restart DOAC between 7 to 14 days of clinical hemostasis after GI bleeding
Sponsored by
About this trial
This is an interventional treatment trial for GastroIntestinal Bleeding
Eligibility Criteria
Inclusion Criteria:
- Male or female subjects aged 18 years or older
- Hospitalized with acute major non-variceal GI bleeding (defined as per ISTH criteria) while receiving OAC therapy (warfarin or DOAC).
- OAC therapy discontinued for current acute GI bleed and not yet resumed
- Ongoing indication for long-term anticoagulation of atrial fibrillation (moderate to high risk of stroke/systemic embolism with CHA2DS2VASc score of 3 or higher) or VTE (as per clinical care team)
- Planned to resume DOAC post-bleed
- At moderate to high risk of re-bleeding as per clinical care team
- Clinical hemostasis achieved as per clinical care team
- Able and willing to comply with follow-up examinations contained within the consent form
Exclusion Criteria:
- Mechanical heart valve
- VTE in the context of major transient risk factor and completed 3 months of treatment
- GI bleeding managed surgically (e.g. gastrectomy, colectomy)
- Active or previously treated gastrointestinal cancer
- Life expectancy from other causes of less than 3 months
- Platelet count < 50,000/µL (or < 50x109/L)
- Renal dysfunction (Creatine Clearance <30 mL/min as calculated by the Cockcroft-Gault formula)
Sites / Locations
- Ottawa Hospital Research Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
High thrombotic risk
Moderate thrombotic risk
Arm Description
For patients at high thrombotic risk, DOACs will be resumed within 7 days of clinical hemostasis after GI bleeding.
For patients at moderate thrombotic risk, DOACs will be resumed between 7 and 14 days of clinical hemostasis after GI bleeding.
Outcomes
Primary Outcome Measures
Recruitment rate
The pilot study will be considered a success and to have demonstrated feasibility if average recruitment of 2 patients per month at each site is achieved.
Total recruitment
Feasibility criterion of achieving recruitment of 85% of the target sample size of 100 patients
Secondary Outcome Measures
eligibility
proportion of patients screened who are eligible to participate out of all patients screened
consent
proportion of eligible patients who provide consent to participate out of all eligible patients
completion of all required study procedures
proportion of patients who complete all required study procedures out of all enrolled patients
adherence
proportion of patients who adhere to study treatment strategy (i.e. resumed DOAC within the specified timeframe) out of the total number of patients enrolled
repeat endoscopy
proportion of patients with repeat endoscopy for suspected bleeding after index GI bleed out of all enrolled patients
re-hospitalization
number of patients re-hospitalization for GI bleeding after index GI bleed out of all patients enrolled
major bleeding
number of patients with major bleeding (as per International Society on Thrombosis and Haemostasis [ISTH] criteria) out of all patients enrolled
clinically relevant non-major bleeding
number of patients with clinically relevant non-major bleeding (CRNMB; as per ISTH) out of all patients enrolled
acute ischemic stroke, transient ischemic attack or systemic embolism
number of patients who experience composite of acute ischemic stroke, transient ischemic attack or systemic embolism our of all patients enrolled
acute symptomatic VTE
number of patients with acute objectively confirmed venous thromboembolism (symptomatic proximal lower extremity deep vein thrombosis [DVT], symptomatic pulmonary embolism [PE] as per ISTH) out of all patients enrolled
net clinical benefit outcome rate
number of patients experiencing composite of stroke, systemic embolic event, major bleeding, or death from any cause out of all patients enrolled
all-cause mortality
number of patients who die of all causes out of all patients enrolled
functional status
Change in functional status measured using Standard Assessment of Global Activities in the Elderly (SAGE) scale at 90 days compared to baseline.
SAGE is a 15-item scale that represents a measure of activities of daily living (ADL) across the spectrum of functioning (cognitive, instrumental and basic ADL). The SAGE is supplemented with additional measures of cognition, mood, and quality of life.
The minimum SAGE score - which corresponds to no functional impairments - is 0. The maximum SAGE score - which corresponds to severe global functional impairment - is 45.
quality of life
Quality of life measured using EuroQol-5D [EQ-5D®] at 90 days compared to baseline.
The EQ-5D instrument comprises a descriptive system questionnaire and a visual analogue scale (EQ VAS). The questionnaire provides a descriptive profile of a respondent's health state representing the level of reported problems on each of the five dimensions of health (mobility, self-care, usual activities, pain or discomfort, anxiety/depression) that can be converted into a single index value. Average index values (expressed as mean and standard deviation or median and interquartile range depending on skewness) at 90 days will be compared to baseline.
The EQ VAS elicits an individual's rating of their own overall current health (0-100 scale where 0 is the worst health you can imagine and 100 is best health you can imagine). Average EQ VAS ratings (expressed as mean and standard deviation or median and interquartile range depending on skewness) at 90 days will be compared to baseline.
Full Information
NCT ID
NCT05290857
First Posted
February 6, 2022
Last Updated
March 21, 2022
Sponsor
Ottawa Hospital Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT05290857
Brief Title
Anticoagulation After GI Bleeding Pilot Study and Registry
Acronym
PANTHER-GI
Official Title
Post-Bleed Management of Antithrombotic Therapy After Gastrointestinal Bleeding: Pilot Study and Registry (PANTHER-GI)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
March 2022 (Anticipated)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Hospital Research Institute
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
PANTHER-GI Pilot Study will assess the feasibility of a full-scale multicentre cohort management study evaluating the safety of a standardized strategy for resuming direct oral anticoagulants (DOACs) after major DOAC-related gastrointestinal (GI) bleeding among patients at moderate to high risk of re-bleeding and thrombosis. A parallel registry will assess whether eligible patients who are not enrolled in the PANTHER-GI Pilot Study are systematically different than enrolled patients and to explore barriers to enrolment.
Detailed Description
This pilot cohort management study will evaluate a protocolized strategy for resuming DOACs after major GI bleeding based on thrombotic risk among patients at moderate to high risk of rebleeding. The timeframe for resuming DOACs will be determined based on the patient's underlying thrombotic risk.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
GastroIntestinal Bleeding, Anticoagulant-induced Bleeding
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
prospective, multicenter, cohort management study and parallel registry
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
High thrombotic risk
Arm Type
Experimental
Arm Description
For patients at high thrombotic risk, DOACs will be resumed within 7 days of clinical hemostasis after GI bleeding.
Arm Title
Moderate thrombotic risk
Arm Type
Experimental
Arm Description
For patients at moderate thrombotic risk, DOACs will be resumed between 7 and 14 days of clinical hemostasis after GI bleeding.
Intervention Type
Other
Intervention Name(s)
Restart DOAC within 7 days of clinical hemostasis after GI bleeding
Intervention Description
In patients at high thrombotic risk, DOACs will be resumed within 7 days of clinical hemostasis (as judged by the clinical team).
High thrombotic risk includes the following:
(i) Atrial fibrillation or atrial flutter with CHA2DS2VASc score of 5 or higher (ii) Atrial fibrillation or atrial flutter with CHA2DS2VASc score or 3 to 4 with recent ischemic stroke, TIA or systemic embolism (within 6 months) (iii) VTE (proximal DVT or PE) within 3 months (iv) Recurrent VTE (proximal DVT or PE) (v) VTE (proximal DVT or PE) associated with antiphospholipid syndrome (if eligible for DOAC) (vi) VTE (proximal DVT or PE) associated with active non-GI cancer (vii) None of the above but considered high thrombotic risk as per investigator
Intervention Type
Other
Intervention Name(s)
Restart DOAC between 7 to 14 days of clinical hemostasis after GI bleeding
Intervention Description
In patients at moderate thrombotic risk, DOACs will be resumed between 7 and 14 days of clinical hemostasis (as judged by the clinical team).
Moderate thrombotic risk includes the following:
(i) Atrial fibrillation or atrial flutter with CHA2DS2VASc score of 3 to 4 (ii) VTE (proximal DVT or PE) beyond 3 months
The type and dose of DOAC will be according to patient and physician choice and will be prescribed by the clinical care team.
Primary Outcome Measure Information:
Title
Recruitment rate
Description
The pilot study will be considered a success and to have demonstrated feasibility if average recruitment of 2 patients per month at each site is achieved.
Time Frame
18 months
Title
Total recruitment
Description
Feasibility criterion of achieving recruitment of 85% of the target sample size of 100 patients
Time Frame
18 months
Secondary Outcome Measure Information:
Title
eligibility
Description
proportion of patients screened who are eligible to participate out of all patients screened
Time Frame
18 months
Title
consent
Description
proportion of eligible patients who provide consent to participate out of all eligible patients
Time Frame
18 months
Title
completion of all required study procedures
Description
proportion of patients who complete all required study procedures out of all enrolled patients
Time Frame
18 months
Title
adherence
Description
proportion of patients who adhere to study treatment strategy (i.e. resumed DOAC within the specified timeframe) out of the total number of patients enrolled
Time Frame
18 months
Title
repeat endoscopy
Description
proportion of patients with repeat endoscopy for suspected bleeding after index GI bleed out of all enrolled patients
Time Frame
90 days
Title
re-hospitalization
Description
number of patients re-hospitalization for GI bleeding after index GI bleed out of all patients enrolled
Time Frame
90 days
Title
major bleeding
Description
number of patients with major bleeding (as per International Society on Thrombosis and Haemostasis [ISTH] criteria) out of all patients enrolled
Time Frame
90 days
Title
clinically relevant non-major bleeding
Description
number of patients with clinically relevant non-major bleeding (CRNMB; as per ISTH) out of all patients enrolled
Time Frame
90 days
Title
acute ischemic stroke, transient ischemic attack or systemic embolism
Description
number of patients who experience composite of acute ischemic stroke, transient ischemic attack or systemic embolism our of all patients enrolled
Time Frame
90 days
Title
acute symptomatic VTE
Description
number of patients with acute objectively confirmed venous thromboembolism (symptomatic proximal lower extremity deep vein thrombosis [DVT], symptomatic pulmonary embolism [PE] as per ISTH) out of all patients enrolled
Time Frame
90 days
Title
net clinical benefit outcome rate
Description
number of patients experiencing composite of stroke, systemic embolic event, major bleeding, or death from any cause out of all patients enrolled
Time Frame
90 days
Title
all-cause mortality
Description
number of patients who die of all causes out of all patients enrolled
Time Frame
90 days
Title
functional status
Description
Change in functional status measured using Standard Assessment of Global Activities in the Elderly (SAGE) scale at 90 days compared to baseline.
SAGE is a 15-item scale that represents a measure of activities of daily living (ADL) across the spectrum of functioning (cognitive, instrumental and basic ADL). The SAGE is supplemented with additional measures of cognition, mood, and quality of life.
The minimum SAGE score - which corresponds to no functional impairments - is 0. The maximum SAGE score - which corresponds to severe global functional impairment - is 45.
Time Frame
90 days
Title
quality of life
Description
Quality of life measured using EuroQol-5D [EQ-5D®] at 90 days compared to baseline.
The EQ-5D instrument comprises a descriptive system questionnaire and a visual analogue scale (EQ VAS). The questionnaire provides a descriptive profile of a respondent's health state representing the level of reported problems on each of the five dimensions of health (mobility, self-care, usual activities, pain or discomfort, anxiety/depression) that can be converted into a single index value. Average index values (expressed as mean and standard deviation or median and interquartile range depending on skewness) at 90 days will be compared to baseline.
The EQ VAS elicits an individual's rating of their own overall current health (0-100 scale where 0 is the worst health you can imagine and 100 is best health you can imagine). Average EQ VAS ratings (expressed as mean and standard deviation or median and interquartile range depending on skewness) at 90 days will be compared to baseline.
Time Frame
90 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female subjects aged 18 years or older
Hospitalized with acute major non-variceal GI bleeding (defined as per ISTH criteria) while receiving OAC therapy (warfarin or DOAC).
OAC therapy discontinued for current acute GI bleed and not yet resumed
Ongoing indication for long-term anticoagulation of atrial fibrillation (moderate to high risk of stroke/systemic embolism with CHA2DS2VASc score of 3 or higher) or VTE (as per clinical care team)
Planned to resume DOAC post-bleed
At moderate to high risk of re-bleeding as per clinical care team
Clinical hemostasis achieved as per clinical care team
Able and willing to comply with follow-up examinations contained within the consent form
Exclusion Criteria:
Mechanical heart valve
VTE in the context of major transient risk factor and completed 3 months of treatment
GI bleeding managed surgically (e.g. gastrectomy, colectomy)
Active or previously treated gastrointestinal cancer
Life expectancy from other causes of less than 3 months
Platelet count < 50,000/µL (or < 50x109/L)
Renal dysfunction (Creatine Clearance <30 mL/min as calculated by the Cockcroft-Gault formula)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Deborah M Siegal, MD
Phone
613-737-8899
Ext
78804
Email
dsiegal@toh.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Deborah M Siegal, MD MSc
Organizational Affiliation
Ottawa Hospital Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ottawa Hospital Research Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H8L6
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
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Anticoagulation After GI Bleeding Pilot Study and Registry
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