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

Official title

Reducing Gastrointestinal Bleeding With Proton Pump Inhibitor Therapy in Acute Venous Thromboembolism: Pilot Randomized Study (RADIANT Study)

Overview

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

Interventions

• Drug Omeprazole 20 mg Oral Tablet
  Omeprazole once daily for 90 days
• Other Placebo
  Placebo once daily for 90 days

Primary outcome measures

• Study feasibility at participating centres [Time frame: 24 months]

Secondary outcome measures (4)

• Eligibility Rate [Time frame: 24 months]
• Consent Rate [Time frame: 24 months]
• Retention Rate [Time frame: 27 months]
• Adherence Rate [Time frame: 27 months]

Eligibility criteria

Inclusion criteria

• 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.
• Newly diagnosed VTE 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.
• Planned for 3 months (90 days) or more of therapeutic anticoagulation with any anticoagulant.
• Patient or delegate is able and willing to comply with follow-up examinations contained within the consent form.

Exclusion criteria

• Therapeutic anticoagulation therapy for more than 7 days
• Currently prescribed PPI for regular daily use (patients receiving H2 receptor antagonists will not be excluded),
• Previous upper GI bleeding,
• Need for dual antiplatelet therapy,
• Contraindications to omeprazole (hypersensitivity to omeprazole, or other substituted benzimidazole PPIs, concomitant use with products that contain rilpivirine, significant drug interactions, up to the discretion of the site investigator),
• Life expectancy is less than 3 months.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Canada · 7 centers

• The Ottawa Hospital — Ottawa
• Niagara Health System - St. Catharines Site — St. Catharines
• University Health Network - Toronto General — Toronto
• CIUSSS de l'Est-de- l'Île-de-Montréal — Montreal
• Centre hospitalier de l'Université de Montréal — Montreal
• CHU de Québec-Université Laval; Hôpital Saint-François d'Assise — Québec
• Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval — Québec

Publications

• Wendelboe AM, McCumber M, Hylek EM, Buller H, Weitz JI, Raskob G; ISTH Steering Committee for World Thrombosis Day. Global public awareness of venous thromboembolism. J Thromb Haemost. 2015 Aug;13(8):1365-71. doi: 10.1111/jth.13031. Epub 2015 Jul 14. PMID 26084415
• Delluc A, Tromeur C, Le Ven F, Gouillou M, Paleiron N, Bressollette L, Nonent M, Salaun PY, Lacut K, Leroyer C, Le Gal G, Couturaud F, Mottier D; EPIGETBO study group. Current incidence of venous thromboembolism and comparison with 1998: a community-based study in Western France. Thromb Haemost. 2016 Oct 28;116(5):967-974. doi: 10.1160/TH16-03-0205. Epub 2016 Jul 28. PMID 27465905
• Heit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol. 2015 Aug;12(8):464-74. doi: 10.1038/nrcardio.2015.83. Epub 2015 Jun 16. PMID 26076949
• Heit JA, Spencer FA, White RH. The epidemiology of venous thromboembolism. J Thromb Thrombolysis. 2016 Jan;41(1):3-14. doi: 10.1007/s11239-015-1311-6. PMID 26780736
• Ferrazzini E, Mean M, Stalder O, Limacher A, Rodondi N, Aujesky D. Incidence and clinical impact of bleeding events in older patients with acute venous thromboembolism. Blood Adv. 2023 Jan 24;7(2):205-213. doi: 10.1182/bloodadvances.2022007263. PMID 35381071
• Hlavacek P, Guo JD, Rosenblatt L, Keshishian A, Russ C, Mardekian J, Ferri M, Poretta T, Yuce H, McBane R. Safety, effectiveness, and health care cost comparisons among elderly patients with venous thromboembolism prescribed warfarin or apixaban in the United States Medicare population. Curr Med Res Opin. 2019 Dec;35(12):2043-2051. doi: 10.1080/03007995.2019.1653067. Epub 2019 Sep 3. PMID 31387467
• Linkins LA, Choi PT, Douketis JD. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. Ann Intern Med. 2003 Dec 2;139(11):893-900. doi: 10.7326/0003-4819-139-11-200312020-00007. PMID 14644891
• Aryal MR, Gosain R, Donato A, Yu H, Katel A, Bhandari Y, Dhital R, Kouides PA. Systematic review and meta-analysis of the efficacy and safety of apixaban compared to rivaroxaban in acute VTE in the real world. Blood Adv. 2019 Aug 13;3(15):2381-2387. doi: 10.1182/bloodadvances.2019000572. PMID 31405948

Identifiers

NCT: NCT06393868 · RADIANT-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗