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

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.

Timeline

Start

2024-11-06

Primary completion

2027-12

Completion

2028-03

Publications

• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background Sindet-Pedersen C, Staerk L, Pallisgaard JL, Gerds TA, Berger JS, Torp-Pedersen C, Gislason GH, Olesen JB. Safety and effectiveness of rivaroxaban and apixaban in patients with venous thromboembolism: a nationwide study. Eur Heart J Cardiovasc Pharmacother. 2018 Oct 1;4(4):220-227. doi: 10.1093/ehjcvp/pvy021.
• Background Catella J, Bertoletti L, Moustafa F, Nieto JA, Valle R, Pedrajas JM, Villalobos A, Quere I, Sarlon-Bartoli G, Monreal M; RIETE Investigators. Major gastrointestinal bleeding in patients receiving anticoagulant therapy for venous thromboembolism. Thromb Res. 2022 Jun;214:29-36. doi: 10.1016/j.thromres.2022.04.005. Epub 2022 Apr 13.
• Background Dawwas GK, Leonard CE, Lewis JD, Cuker A. Risk for Recurrent Venous Thromboembolism and Bleeding With Apixaban Compared With Rivaroxaban: An Analysis of Real-World Data. Ann Intern Med. 2022 Jan;175(1):20-28. doi: 10.7326/M21-0717. Epub 2021 Dec 7.
• Background Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, Mismetti P, Christiansen AV, Friedman J, Le Maulf F, Peter N, Kearon C; RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014 Feb 18;129(7):764-72. doi: 10.1161/CIRCULATIONAHA.113.004450. Epub 2013 Dec 16.
• Background Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, Kvamme AM, Friedman J, Mismetti P, Goldhaber SZ; RE-MEDY Trial Investigators; RE-SONATE Trial Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):709-18. doi: 10.1056/NEJMoa1113697.
• Background Hokusai-VTE Investigators; Buller HR, Decousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013 Oct 10;369(15):1406-15. doi: 10.1056/NEJMoa1306638. Epub 2013 Aug 31.
• Background Prins MH, Lensing AW, Bauersachs R, van Bellen B, Bounameaux H, Brighton TA, Cohen AT, Davidson BL, Decousus H, Raskob GE, Berkowitz SD, Wells PS; EINSTEIN Investigators. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J. 2013 Sep 20;11(1):21. doi: 10.1186/1477-9560-11-21.
• Background Wells PS, Prins MH, Levitan B, Beyer-Westendorf J, Brighton TA, Bounameaux H, Cohen AT, Davidson BL, Prandoni P, Raskob GE, Yuan Z, Katz EG, Gebel M, Lensing AWA. Long-term Anticoagulation With Rivaroxaban for Preventing Recurrent VTE: A Benefit-Risk Analysis of EINSTEIN-Extension. Chest. 2016 Nov;150(5):1059-1068. doi: 10.1016/j.chest.2016.05.023. Epub 2016 Jun 1.
• Background Agnelli G, Becattini C, Meyer G, Munoz A, Huisman MV, Connors JM, Cohen A, Bauersachs R, Brenner B, Torbicki A, Sueiro MR, Lambert C, Gussoni G, Campanini M, Fontanella A, Vescovo G, Verso M; Caravaggio Investigators. Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. N Engl J Med. 2020 Apr 23;382(17):1599-1607. doi: 10.1056/NEJMoa1915103. Epub 2020 Mar 29.
• Background Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Porcari A, Raskob GE, Weitz JI; AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):699-708. doi: 10.1056/NEJMoa1207541. Epub 2012 Dec 8.
• Background Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013 Aug 29;369(9):799-808. doi: 10.1056/NEJMoa1302507. Epub 2013 Jul 1.
• Background Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, Hale D, Dunn JA, Lyman GH, Hutchinson C, MacCallum P, Kakkar A, Hobbs FDR, Petrou S, Dale J, Poole CJ, Maraveyas A, Levine M. Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D). J Clin Oncol. 2018 Jul 10;36(20):2017-2023. doi: 10.1200/JCO.2018.78.8034. Epub 2018 May 10.
• Background Raskob G, Buller H, Prins M, Segers A, Shi M, Schwocho L, van Kranen R, Mercuri M; Hokusai-VTE Investigators. Edoxaban for the long-term treatment of venous thromboembolism: rationale and design of the Hokusai-venous thromboembolism study--methodological implications for clinical trials. J Thromb Haemost. 2013 Jul;11(7):1287-94. doi: 10.1111/jth.12230.
• Background Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, Nelson ME, Wells PS, Gould MK, Dentali F, Crowther M, Kahn SR. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e419S-e496S. doi: 10.1378/chest.11-2301.
• Background Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang TF, Yeo E, Zhang G, Zwicker JI, Weitz JI, Buller HR; Hokusai VTE Cancer Investigators. Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism. N Engl J Med. 2018 Feb 15;378(7):615-624. doi: 10.1056/NEJMoa1711948. Epub 2017 Dec 12.
• Background Douketis JD, Foster GA, Crowther MA, Prins MH, Ginsberg JS. Clinical risk factors and timing of recurrent venous thromboembolism during the initial 3 months of anticoagulant therapy. Arch Intern Med. 2000 Dec 11-25;160(22):3431-6. doi: 10.1001/archinte.160.22.3431.
• Background Gitter MJ, Jaeger TM, Petterson TM, Gersh BJ, Silverstein MD. Bleeding and thromboembolism during anticoagulant therapy: a population-based study in Rochester, Minnesota. Mayo Clin Proc. 1995 Aug;70(8):725-33. doi: 10.4065/70.8.725.
• Background Carrier M, Le Gal G, Wells PS, Rodger MA. Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism. Ann Intern Med. 2010 May 4;152(9):578-89. doi: 10.7326/0003-4819-152-9-201005040-00008.
• Background Connolly SJ, Crowther M, Eikelboom JW, Gibson CM, Curnutte JT, Lawrence JH, Yue P, Bronson MD, Lu G, Conley PB, Verhamme P, Schmidt J, Middeldorp S, Cohen AT, Beyer-Westendorf J, Albaladejo P, Lopez-Sendon J, Demchuk AM, Pallin DJ, Concha M, Goodman S, Leeds J, Souza S, Siegal DM, Zotova E, Meeks B, Ahmad S, Nakamya J, Milling TJ Jr; ANNEXA-4 Investigators. Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. 2019 Apr 4;380(14):1326-1335. doi: 10.1056/NEJMoa1814051. Epub 2019 Feb 7.
• Background Pollack CV Jr, Reilly PA, Weitz JI. Dabigatran Reversal with Idarucizumab. N Engl J Med. 2017 Oct 26;377(17):1691-2. doi: 10.1056/NEJMc1711337. No abstract available.
• Background Held C, Hylek EM, Alexander JH, Hanna M, Lopes RD, Wojdyla DM, Thomas L, Al-Khalidi H, Alings M, Xavier D, Ansell J, Goto S, Ruzyllo W, Rosenqvist M, Verheugt FW, Zhu J, Granger CB, Wallentin L. Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial. Eur Heart J. 2015 May 21;36(20):1264-72. doi: 10.1093/eurheartj/ehu463. Epub 2014 Dec 12.
• Background Klok FA, Niemann C, Dellas C, Hasenfuss G, Konstantinides S, Lankeit M. Performance of five different bleeding-prediction scores in patients with acute pulmonary embolism. J Thromb Thrombolysis. 2016 Feb;41(2):312-20. doi: 10.1007/s11239-015-1239-x.
• Background Klok FA, Hosel V, Clemens A, Yollo WD, Tilke C, Schulman S, Lankeit M, Konstantinides SV. Prediction of bleeding events in patients with venous thromboembolism on stable anticoagulation treatment. Eur Respir J. 2016 Nov;48(5):1369-1376. doi: 10.1183/13993003.00280-2016. Epub 2016 Jul 28.
• Background Thomopoulos KC, Mimidis KP, Theocharis GJ, Gatopoulou AG, Kartalis GN, Nikolopoulou VN. Acute upper gastrointestinal bleeding in patients on long-term oral anticoagulation therapy: endoscopic findings, clinical management and outcome. World J Gastroenterol. 2005 Mar 7;11(9):1365-8. doi: 10.3748/wjg.v11.i9.1365.
• Background Morin J, Alayche M, Ghossein J, Delluc C, Siegal D, Wang TF, Delluc A. Source of upper gastrointestinal bleeding in cancer patients: A cross-sectional study. Thromb Res. 2022 Sep;217:9-11. doi: 10.1016/j.thromres.2022.06.009. Epub 2022 Jul 1. No abstract available.
• Background Deitelzweig S, Keshishian A, Kang A, Dhamane AD, Luo X, Balachander N, Rosenblatt L, Mardekian J, Jiang J, Yuce H, Lip GYH. Burden of major gastrointestinal bleeding among oral anticoagulant-treated non-valvular atrial fibrillation patients. Ther Adv Gastroenterol. 2021 Mar 21;14:1756284821997352. doi: 10.1177/1756284821997352. eCollection 2021.
• Background Sherwood MW, Nessel CC, Hellkamp AS, Mahaffey KW, Piccini JP, Suh EY, Becker RC, Singer DE, Halperin JL, Hankey GJ, Berkowitz SD, Fox KAA, Patel MR. Gastrointestinal Bleeding in Patients With Atrial Fibrillation Treated With Rivaroxaban or Warfarin: ROCKET AF Trial. J Am Coll Cardiol. 2015 Dec 1;66(21):2271-2281. doi: 10.1016/j.jacc.2015.09.024.
• Background Candeloro M, van Es N, Cantor N, Schulman S, Carrier M, Ageno W, Aibar J, Donadini MP, Bavalia R, Arsenault MP, Coppens M, Ferrante N, D'Addezio A, Sormani S, Porreca E, Di Nisio M. Recurrent bleeding and thrombotic events after resumption of oral anticoagulants following gastrointestinal bleeding: Communication from the ISTH SSC Subcommittee on Control of Anticoagulation. J Thromb Haemost. 2021 Oct;19(10):2618-2628. doi: 10.1111/jth.15476. Epub 2021 Aug 8.
• Background Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014 Mar 15;383(9921):955-62. doi: 10.1016/S0140-6736(13)62343-0. Epub 2013 Dec 4.
• Background Schulman S, Gross PL, Ritchie B, Nahirniak S, Lin Y, Lieberman L, Carrier M, Crowther MA, Ghosh I, Lazo-Langner A, Zondag M; Study Investigators. Prothrombin Complex Concentrate for Major Bleeding on Factor Xa Inhibitors: A Prospective Cohort Study. Thromb Haemost. 2018 May;118(5):842-851. doi: 10.1055/s-0038-1636541. Epub 2018 Mar 21.
• Background Majeed A, Agren A, Holmstrom M, Bruzelius M, Chaireti R, Odeberg J, Hempel EL, Magnusson M, Frisk T, Schulman S. Management of rivaroxaban- or apixaban-associated major bleeding with prothrombin complex concentrates: a cohort study. Blood. 2017 Oct 12;130(15):1706-1712. doi: 10.1182/blood-2017-05-782060. Epub 2017 Aug 23.
• Background Gomez-Outes A, Alcubilla P, Calvo-Rojas G, Terleira-Fernandez AI, Suarez-Gea ML, Lecumberri R, Vargas-Castrillon E. Meta-Analysis of Reversal Agents for Severe Bleeding Associated With Direct Oral Anticoagulants. J Am Coll Cardiol. 2021 Jun 22;77(24):2987-3001. doi: 10.1016/j.jacc.2021.04.061.
• Background Nieto JA, Solano R, Ruiz-Ribo MD, Ruiz-Gimenez N, Prandoni P, Kearon C, Monreal M; Riete Investigators. Fatal bleeding in patients receiving anticoagulant therapy for venous thromboembolism: findings from the RIETE registry. J Thromb Haemost. 2010 Jun;8(6):1216-22. doi: 10.1111/j.1538-7836.2010.03852.x. Epub 2010 Mar 12.
• Background Little DHW, Sutradhar R, Cerasuolo JO, Perez R, Douketis J, Holbrook A, Paterson JM, Gomes T, Siegal DM. Rates of rebleeding, thrombosis and mortality associated with resumption of anticoagulant therapy after anticoagulant-related bleeding. CMAJ. 2021 Mar 1;193(9):E304-E309. doi: 10.1503/cmaj.201433.
• Background Little D, Chai-Adisaksopha C, Hillis C, Witt DM, Monreal M, Crowther MA, Siegal DM. Resumption of anticoagulant therapy after anticoagulant-related gastrointestinal bleeding: A systematic review and meta-analysis. Thromb Res. 2019 Mar;175:102-109. doi: 10.1016/j.thromres.2019.01.020. Epub 2019 Jan 30.
• Background Wang K, Li H, Kwong WJ, Antman EM, Ruff CT, Giugliano RP, Cohen DJ, Magnuson EA; ENGAGE AF-TIMI 48 Trial Investigators. Impact of Spontaneous Extracranial Bleeding Events on Health State Utility in Patients with Atrial Fibrillation: Results from the ENGAGE AF-TIMI 48 Trial. J Am Heart Assoc. 2017 Aug 11;6(8):e006703. doi: 10.1161/JAHA.117.006703.
• Background Targownik LE, Fisher DA, Saini SD. AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review. Gastroenterology. 2022 Apr;162(4):1334-1342. doi: 10.1053/j.gastro.2021.12.247. Epub 2022 Feb 17.
• Background Barkun AN, Almadi M, Kuipers EJ, Laine L, Sung J, Tse F, Leontiadis GI, Abraham NS, Calvet X, Chan FKL, Douketis J, Enns R, Gralnek IM, Jairath V, Jensen D, Lau J, Lip GYH, Loffroy R, Maluf-Filho F, Meltzer AC, Reddy N, Saltzman JR, Marshall JK, Bardou M. Management of Nonvariceal Upper Gastrointestinal Bleeding: Guideline Recommendations From the International Consensus Group. Ann Intern Med. 2019 Dec 3;171(11):805-822. doi: 10.7326/M19-1795. Epub 2019 Oct 22.
• Background Moayyedi P, Eikelboom JW, Bosch J, Connolly SJ, Dyal L, Shestakovska O, Leong D, Anand SS, Stork S, Branch KRH, Bhatt DL, Verhamme PB, O'Donnell M, Maggioni AP, Lonn EM, Piegas LS, Ertl G, Keltai M, Cook Bruns N, Muehlhofer E, Dagenais GR, Kim JH, Hori M, Steg PG, Hart RG, Diaz R, Alings M, Widimsky P, Avezum A, Probstfield J, Zhu J, Liang Y, Lopez-Jaramillo P, Kakkar A, Parkhomenko AN, Ryden L, Pogosova N, Dans A, Lanas F, Commerford PJ, Torp-Pedersen C, Guzik T, Vinereanu D, Tonkin AM, Lewis BS, Felix C, Yusoff K, Metsarinne K, Fox KAA, Yusuf S; COMPASS Investigators. Pantoprazole to Prevent Gastroduodenal Events in Patients Receiving Rivaroxaban and/or Aspirin in a Randomized, Double-Blind, Placebo-Controlled Trial. Gastroenterology. 2019 Aug;157(2):403-412.e5. doi: 10.1053/j.gastro.2019.04.041. Epub 2019 May 2.
• Background Dong Y, He S, Li X, Zhou Z. Prevention of nNon-Vitamin K Oral Anticoagulants-Related Gastrointestinal Bleeding With Acid Suppressants: A Systematic Review and Meta-Analysis. Clin Appl Thromb Hemost. 2022 Jan-Dec;28:10760296211064897. doi: 10.1177/10760296211064897.
• Background Bang CS, Joo MK, Kim BW, Kim JS, Park CH, Ahn JY, Lee JH, Lee BE, Yang HJ, Cho YK, Park JM, Kim BJ, Jung HK; Korean College of Helicobacter and Upper Gastrointestinal Research. The Role of Acid Suppressants in the Prevention of Anticoagulant-Related Gastrointestinal Bleeding: A Systematic Review and Meta-Analysis. Gut Liver. 2020 Jan 15;14(1):57-66. doi: 10.5009/gnl19009.
• Background Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.
• Background Kaatz S, Ahmad D, Spyropoulos AC, Schulman S; Subcommittee on Control of Anticoagulation. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost. 2015 Nov;13(11):2119-26. doi: 10.1111/jth.13140. No abstract available.
• Background Rabin R, de Charro F. EQ-5D: a measure of health status from the EuroQol Group. Ann Med. 2001 Jul;33(5):337-43. doi: 10.3109/07853890109002087.
• Background Spence J, Bosch J, Chongsi E, Lee SF, Thabane L, Mendoza P, Belley-Cote E, Whitlock R, Brady K, McIntyre WF, Lamy A, Devereaux PJ. Standardized Assessment of Global activities in the Elderly scale in adult cardiac surgery patients. Br J Anaesth. 2021 Oct;127(4):539-546. doi: 10.1016/j.bja.2021.05.037. Epub 2021 Jul 28.
• Background Forbes N, Elmunzer BJ, Keswani RN, Hilsden RJ, Hall M, Anderson JT, Arvanitakis M, Chen YI, Duloy A, Elta GH, Maranki JL, Mergener K, Petersen BT, Sethi A, Siersema PD, Smith ZL, Telford JJ, Tse F, Cotton PB, Wani S. Consensus-based development of a causal attribution system for post-ERCP adverse events. Gut. 2022 Jul 11:gutjnl-2022-328059. doi: 10.1136/gutjnl-2022-328059. Online ahead of print. No abstract available.
• Background Hilsden RJ, Maxwell CM, Forbes N, Bridges RJ, Rostom A, Dube C, Boyne D, Brenner D, Heitman SJ. Development of a definition and rules for causal attribution of post-colonoscopy bleeding. PLoS One. 2020 Jul 23;15(7):e0235902. doi: 10.1371/journal.pone.0235902. eCollection 2020.
• Background Le Gal G, Carrier M, Castellucci LA, Cuker A, Hansen JB, Klok FA, Langlois NJ, Levy JH, Middeldorp S, Righini M, Walters S; ISTH CDE Task Force. Development and implementation of common data elements for venous thromboembolism research: on behalf of SSC Subcommittee on official Communication from the SSC of the ISTH. J Thromb Haemost. 2021 Jan;19(1):297-303. doi: 10.1111/jth.15138.

Drugs

Indications