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Reducing Gastrointestinal Bleeding With Proton Pump Inhibitor Therapy in Acute Venous Thromboembolism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT06393868
Recruitment Status : Not yet recruiting
First Posted : May 1, 2024
Last Update Posted : May 1, 2024
Sponsor:
Information provided by (Responsible Party):
Deborah Siegal, Ottawa Hospital Research Institute

Tracking Information
First Submitted Date  ICMJE March 19, 2024
First Posted Date  ICMJE May 1, 2024
Last Update Posted Date May 1, 2024
Estimated Study Start Date  ICMJE June 2024
Estimated Primary Completion Date September 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 26, 2024)		 Study feasibility at participating centres [ Time Frame: 24 months ]
The mean number of participants recruited per site per month
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2024)
  • Eligibility Rate [ Time Frame: 24 months ]
    Proportion of screened patients who are eligible
  • Consent Rate [ Time Frame: 24 months ]
    Proportion of eligible patients who provide consent
  • Retention Rate [ Time Frame: 27 months ]
    Proportion of participants who completed all study procedures
  • Adherence Rate [ Time Frame: 27 months ]
    adherence to study drug measured by pill count or assessing the patient diary at the end of follow-up
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: April 26, 2024)
  • Risk Factors [ Time Frame: 24 months ]
    The proportion of participants with the following risk factors for bleeding at baseline: decreased kidney function (defined as estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2), active cancer, concurrent antiplatelet and/or NSAID therapy, chronic liver disease, chronic anemia.
  • Patients already prescribed proton pump inhibitor [ Time Frame: 24 months ]
    The proportion of screened patients already receiving prescribed proton pump inhibitor therapy
  • Reasons for Declining Participation [ Time Frame: 24 months ]
    Patients are not required to provide a reason for declining to participate. However, for those patients who are willing to share, reasons for declining participation will be reviewed
  • New PPI prescription [ Time Frame: 27 months ]
    The proportion of participants with new prescription for proton pump inhibitor during the study
  • Recurrent VTE [ Time Frame: 27 months ]
    The proportion of patients that have a recurrent venous thromboembolism during the study
  • Mortality [ Time Frame: 27 months ]
    The proportion of patients who die from gastrointestinal bleeding, and all-cause mortality during the study
  • Serious Adverse Events [ Time Frame: 27 months ]
    The proportion of patients who have a serious adverse event during the study
  • Change in health-related quality of life [ Time Frame: 27 months ]
    Change in health-related quality of life as measured by the EuroQol EQ-5D-5L Quality of Life questionnaire at 90 days compared to baseline. This questionnaire includes the patient's thoughts about their health, including mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. The lowest possible score is 5 and the highest is 25. A lower score represents a worse quality of life. The questionnaire also includes a Visible Analog Scale where patients are asked to picture a vertical line that is numbered from 0 to 100. 100 at the top of the line means the best health the patient can imagine and 0 at the bottom of the line means the worst health the patient can imagine. Patients are asked to provide a number that best represents their health at the time of completing the questionnaire.
  • Change in functional status [ Time Frame: 27 months ]
    Change in functional status as measured by the Standard Assessment of Global Activities in the Elderly (SAGE) scale at 90 days compared to baseline. The SAGE questionnaire measures what patients are doing in their community and their homes. Patients are asked to indicate the level of difficulty they have with each of the questions in the past month with a response of no difficulty, mild, moderate, or severe difficulty. Mild = minimal/occasional difficulty that does not affect the ability to perform the activity or task; Moderate = some/regular difficulty that does affect the ability to perform the task, although they may still be able to perform the task; Severe = extreme/constant difficulty performing the task or the task is not completed and/or is completed by someone else because of its difficulty.
  • Clinically Relevant Upper Gastrointestinal Bleeding Events [ Time Frame: 27 months ]
    Adjudicated clinically relevant upper gastrointestinal bleeding (major upper gastrointestinal bleeding plus clinically relevant non-major [CRNM] upper GI bleeding, adapted from International Society on Thrombosis and Haemostasis (ISTH) criteria for major bleeding and CRNM bleeding).
  • Rate of endoscopically confirmed upper gastrointestinal bleeding [ Time Frame: 27 months ]
    Proportion of patients who have upper gastrointestinal bleeding as confirmed by endoscope at 30, 60, and 90 days post randomization
  • Rate of lower gastrointestinal bleeding [ Time Frame: 27 months ]
    Proportion of patients who have lower gastrointestinal bleeding at 30, 60, and 90 days post randomization
  • All major gastrointestinal bleeding [ Time Frame: 27 months ]
    Proportion of patients who have confirmed major gastrointestinal bleeding by adjudication at 30, 60, and 90 days post randomization
  • All clinically relevant non-major gastrointestinal bleeding [ Time Frame: 27 months ]
    Proportion of patients who have confirmed clinically relevant non-major gastrointestinal bleeding by adjudication at 30, 60. 90 days
  • All major bleeding [ Time Frame: 27 months ]
    Proportion of patients who have confirmed major bleeding by adjudication, including major GI bleeding) at 30, 60, 90 days post randomization
  • All clinically relevant non-major bleeding [ Time Frame: 27 months ]
    Proportion of patients who have confirmed clinically relevant non-major bleeding (including CRNM GI bleeding) at 30, 60, and 90 days post randomization
  • Hospitalization for gastrointestinal bleeding [ Time Frame: 27 months ]
    Proportion of patients hospitalized for gastrointestinal bleeding at 30, 60. and 90 days post randomization
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Reducing Gastrointestinal Bleeding With Proton Pump Inhibitor Therapy in Acute Venous Thromboembolism
Official Title  ICMJE Reducing Gastrointestinal Bleeding With Proton Pump Inhibitor Therapy in Acute Venous Thromboembolism: Pilot Randomized Study (RADIANT Study)
Brief Summary The investigators are studying whether treatment with a proton pump inhibitor called omeprazole reduces gastrointestinal bleeding in older adults taking blood thinners for a blood clot (venous thromboembolism). The purpose of this study, a pilot study or a feasibility study, is to test the study plan and determine whether enough participants will join a larger study and accept the study procedures.
Detailed Description

Venous thromboembolism (VTE) refers to blood clots that form in the veins of the body, including the arms or legs (deep vein thrombosis [DVT]), abdomen (portal vein thrombosis), or lungs (pulmonary embolism [PE]). These blood clots are treated with medication to reduce blood clotting called anticoagulants. The main complication of anticoagulants is bleeding, the majority of which comes from the stomach or intestines (gastrointestinal tract). Anticoagulants do not cause bleeding, but they may make bleeding worse. Uncommonly, serious gastrointestinal (GI) bleeding can happen leading to hospitalization and even death. The chance of bleeding is highest in the first few months after starting anticoagulants.

Proton pump inhibitors (PPIs) are medications that lower the acid content of the stomach. The medication in this study, a type of proton pump inhibitor called omeprazole, is approved in Canada for treating stomach ulcers, heartburn, and a stomach infection called Helicobacter pylori. The use of omeprazole in this study is considered investigational. This means that Health Canada has not approved the use of omeprazole as a treatment for preventing gastrointestinal bleeding in patients taking anticoagulants. Some studies suggest that they may reduce gastrointestinal bleeding for people taking anticoagulants.

The investigators are studying whether treatment with a proton pump inhibitor called omeprazole reduces gastrointestinal bleeding in older adults taking anticoagulants for venous thromboembolism.

The investigators plan to do a large, randomized trial which is the best way to test the effect of a treatment. To do this, some of the participants in this study will get omeprazole and others will get a placebo (a substance that looks like the study omeprazole but does not have any active or medicinal ingredients). The placebo in this study is not intended to have any effect on bleeding. A placebo is used to make the results of the study more reliable.

Primary Objective To assess the feasibility of a full-scale double-blind placebo-controlled randomized trial to determine whether omeprazole reduces the risk of upper GI bleeding in older adults receiving anticoagulation for acute VTE compared to placebo.

Secondary Objectives:

  1. To measure additional feasibility outcomes
  2. To measure informative outcomes
  3. To measure key clinical outcomes
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Venous Thromboembolism
  • Gastro Intestinal Bleeding
  • Blood Clot
Intervention  ICMJE
  • Drug: Omeprazole 20 mg Oral Tablet
    Omeprazole once daily for 90 days
    Other Name: Omeprazole
  • Other: Placebo
    Placebo once daily for 90 days
Study Arms  ICMJE
  • Experimental: Daily dose of omeprazole 20 mg
    Participants randomized to the experimental arm will take one omeprazole 20 mg tablet by mouth every day for the duration of their participation in the study.
    Intervention: Drug: Omeprazole 20 mg Oral Tablet
  • Placebo Comparator: Daily dose of placebo
    Participants randomized to the control arm will take one placebo tablet by mouth every day for the duration of their participation in the study.
    Intervention: Other: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: April 26, 2024)		 360
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2024
Estimated Primary Completion Date September 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female 65 years or older at the time of enrolment. Enrolment is limited to older adults as age is an important non-modifiable risk factor for bleeding. This will ensure the study population includes participants who may be more likely to benefit from omeprazole (compared to those with no risk factors) because all participants will have at least 1 risk factor for bleeding.
  2. Acute VTE diagnosed within the previous 7 days which includes VTE at any site such as (but not limited to) DVT of upper or lower limbs, PE, cerebral vein thrombosis, portal vein thrombosis, other splanchnic vein thrombosis.
  3. Planned for 3 months (90 days) or more of therapeutic anticoagulation with any anticoagulant.
  4. Patient or delegate is able and willing to comply with follow-up examinations contained within the consent form.

Exclusion Criteria:

  1. Currently prescribed PPI for regular daily use (patients receiving H2 receptor antagonists will not be excluded),
  2. previous upper GI bleeding,
  3. need for dual antiplatelet therapy,
  4. contraindications to omeprazole (hypersensitivity to omeprazole, or other substituted benzimidazole PPIs, concomitant use with products that contain rilpivirine, up to the discretion of the site investigator),
  5. life expectancy is less than 3 months.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 65 Years and older   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Deborah Siegal, MD (613) 737-8899 ext 78804 dsiegal@toh.ca
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT06393868
Other Study ID Numbers  ICMJE RADIANT-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: CONVERGE trials will be conducted within specific research domains under a core protocol outlining shared elements, including broad inclusion criteria, a minimum set of core outcomes, event adjudication, and data sharing to the CONVERGE shared data repository. Patients meeting domain-specific inclusion criteria can be enrolled in individual trials based on pre-defined additional characteristics. RADIANT will be the first trial conducted within the Acute VTE Treatment Domain.
Supporting Materials: Study Protocol
Time Frame: Starting after study completion
Access Criteria: Select members of the International Network of VENous Thromboembolism Clinical Research Networks (INVENT) participating in CONVERGE trials will enter into an agreement to enhance data-sharing and meta-analysis across trials. Access will be restricted by strict authentication processes and data will be maintained on secure servers.
Current Responsible Party Deborah Siegal, Ottawa Hospital Research Institute
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Deborah Siegal
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Deborah Siegal, MD Ottawa Hospital Research Institute
PRS Account Ottawa Hospital Research Institute
Verification Date April 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP