Anticoagulation After GI Bleeding Pilot Study and Registry

GastroIntestinal Bleeding Clinical Trial

— PANTHER-GI  

Official title:

Post-Bleed Management of Antithrombotic Therapy After Gastrointestinal Bleeding: Pilot Study and Registry (PANTHER-GI)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05290857
• Other study ID #: 3349 20210798-01H
• Status: Recruiting
• Phase: N/A
• Start date: March 31, 2022
• Est. completion date: December 2025

Study information

• Verified date: November 2023
• Source: Ottawa Hospital Research Institute
• Contact: Deborah M Siegal, MD
• Phone: 613-737-8899
• Email: dsiegal[@]toh.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female subjects aged 18 years or older

2. Hospitalized with acute major non-variceal GI bleeding (defined as per ISTH criteria) while receiving OAC therapy (warfarin or DOAC).

3. OAC therapy discontinued for current acute GI bleed and not yet resumed

4. 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)

5. Planned to resume DOAC post-bleed

6. At moderate to high risk of re-bleeding as per clinical care team

7. Clinical hemostasis achieved as per clinical care team

8. Able and willing to comply with follow-up examinations contained within the consent form

Exclusion Criteria:

1. Mechanical heart valve

2. VTE in the context of major transient risk factor and completed 3 months of treatment

3. GI bleeding managed surgically (e.g. gastrectomy, colectomy)

4. Active or previously treated gastrointestinal cancer

5. Life expectancy from other causes of less than 3 months

6. Platelet count < 50,000/µL (or < 50x109/L)

7. Renal dysfunction (Creatine Clearance <30 mL/min as calculated by the Cockcroft-Gault formula)

Related Conditions & MeSH terms

• Anticoagulant-induced Bleeding
• GastroIntestinal Bleeding
• Gastrointestinal Hemorrhage
• Hemorrhage

Intervention

Other:
• Restart DOAC within 7 days of clinical hemostasis after GI bleeding
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
• Restart DOAC between 7 to 14 days of clinical hemostasis after GI bleeding
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.

Locations

Country	Name	City	State
Canada	Alberta Health Services - Peter Lougheed Center Endoscopy Unit	Calgary	Alberta
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	18 months
Primary	Total recruitment	Feasibility criterion of achieving recruitment of 85% of the target sample size of 100 patients	18 months
Secondary	eligibility	proportion of patients screened who are eligible to participate out of all patients screened	18 months
Secondary	consent	proportion of eligible patients who provide consent to participate out of all eligible patients	18 months
Secondary	completion of all required study procedures	proportion of patients who complete all required study procedures out of all enrolled patients	18 months
Secondary	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	18 months
Secondary	repeat endoscopy	proportion of patients with repeat endoscopy for suspected bleeding after index GI bleed out of all enrolled patients	90 days
Secondary	re-hospitalization	number of patients re-hospitalization for GI bleeding after index GI bleed out of all patients enrolled	90 days
Secondary	major bleeding	number of patients with major bleeding (as per International Society on Thrombosis and Haemostasis [ISTH] criteria) out of all patients enrolled	90 days
Secondary	clinically relevant non-major bleeding	number of patients with clinically relevant non-major bleeding (CRNMB; as per ISTH) out of all patients enrolled	90 days
Secondary	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	90 days
Secondary	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	90 days
Secondary	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	90 days
Secondary	all-cause mortality	number of patients who die of all causes out of all patients enrolled	90 days
Secondary	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.	90 days
Secondary	Quality of life of Panther GI Research participants	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.	90 days