Proton Pump Inhibitor Versus Histamine-2 Receptor Antagonist for the Prevention of Recurrent Peptic Ulcers

Peptic Ulcer Clinical Trial

Official title:

Pantoprazole Versus Famotidine for the Prevention of Recurrent Peptic Ulcers in Thienopyridine Users — a Double-blind Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02551744
• Other study ID #: VGHKS12-CT7-08
• Status: Completed
• Phase: N/A
• Start date: July 2012
• Est. completion date: July 2018

Study information

• Verified date: June 2019
• Source: Kaohsiung Veterans General Hospital.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Whether pantoprazole versus famotidine for the prevention of recurrent peptic ulcers in thienopyridine users remains unclear.

Description:

The aims of the randomized double-blind comparison study are to compare the efficacy of Proton Pump Inhibitor and H2 receptor antagonist for the prevention of recurrent peptic ulcers in thienopyridine users. We plan to enroll 334 thienopyridine (clopidogrel or ticlopidine) users without baseline gastroduodenal ulcer at initial endoscopy. The patients will be randomly assigned to receive either (1) pantoprazole (40 mg qd) or (2) famotidine (40 mg qd) for 6 months.The ulcer recurrence rate between the treatment groups will be compared.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: July 2018
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 90 Years

Eligibility

Inclusion Criteria:

• Recent endoscopic examination (within 2 months) reveals normal appearance or erythematous patches only (without subepithelial hemorrhages, erosions or ulcers).

• Peptic ulcers (a mucosal break ³ 5 mm in diameter) have been documented by a previous endoscopic examination.

• Subjects have received thienopyridine therapy for at least two weeks.

• Requiring long-term anti-platelet therapy for ischemic cardiovascular diseases.

Exclusion Criteria:

• A history of gastric or duodenal surgery other than oversewing of a perforation.

• Subjects who are allergic to the study drugs.

• Requiring long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, aspirin, or anticoagulant agents.

• Pregnancy.

• Subjects who have active cancer, acute serious medical illness or terminal illness.

• Subjects who have gastroesophageal reflux disease.

Related Conditions & MeSH terms

• Peptic Ulcer
• Ulcer

Intervention

Drug:
• histamine-2 receptor antagonist group
famotidine tab 40 mg qd for 6 months.
• proton pump inhibitor group
pantoprazole tab 40 mg qd for 6 months.

Locations

Country	Name	City	State
Taiwan	Kaohsiung Veterans General Hospital	Kaohsiung

Sponsors (1)

Lead Sponsor	Collaborator
Kaohsiung Veterans General Hospital.

Country where clinical trial is conducted

Taiwan, 

References & Publications (21)

Bhatt DL, Cryer BL, Contant CF, Cohen M, Lanas A, Schnitzer TJ, Shook TL, Lapuerta P, Goldsmith MA, Laine L, Scirica BM, Murphy SA, Cannon CP; COGENT Investigators. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med. 2010 Nov 11;363(20):1909-17. doi: 10.1056/NEJMoa1007964. Epub 2010 Oct 6. — View Citation

Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Brennan DM, Fabry-Ribaudo L, Booth J, Topol EJ; CHARISMA Investigators. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006 Apr 20;354(16):1706-17. Epub 2006 Mar 12. — View Citation

Boeynaems JM, van Giezen H, Savi P, Herbert JM. P2Y receptor antagonists in thrombosis. Curr Opin Investig Drugs. 2005 Mar;6(3):275-82. Review. — View Citation

CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996 Nov 16;348(9038):1329-39. — View Citation

Chan FK, Ching JY, Hung LC, Wong VW, Leung VK, Kung NN, Hui AJ, Wu JC, Leung WK, Lee VW, Lee KK, Lee YT, Lau JY, To KF, Chan HL, Chung SC, Sung JJ. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med. 2005 Jan 20;352(3):238-44. — View Citation

Fork FT, Lafolie P, Tóth E, Lindgärde F. Gastroduodenal tolerance of 75 mg clopidogrel versus 325 mg aspirin in healthy volunteers. A gastroscopic study. Scand J Gastroenterol. 2000 May;35(5):464-9. — View Citation

Ho PM, Maddox TM, Wang L, Fihn SD, Jesse RL, Peterson ED, Rumsfeld JS. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA. 2009 Mar 4;301(9):937-44. doi: 10.1001/jama.2009.261. — View Citation

Hsu PI, Lai KH, Liu CP. Esomeprazole with clopidogrel reduces peptic ulcer recurrence, compared with clopidogrel alone, in patients with atherosclerosis. Gastroenterology. 2011 Mar;140(3):791-8. doi: 10.1053/j.gastro.2010.11.056. Epub 2010 Dec 7. Erratum in: Gastroenterology. 2011 Aug;141(2):778. — View Citation

Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, Henry DA, Kopp A, Mamdani MM. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009 Mar 31;180(7):713-8. doi: 10.1503/cmaj.082001. Epub 2009 Jan 28. — View Citation

Laine L, Hennekens C. Proton pump inhibitor and clopidogrel interaction: fact or fiction? Am J Gastroenterol. 2010 Jan;105(1):34-41. doi: 10.1038/ajg.2009.638. Epub 2009 Nov 10. Review. — View Citation

Laine L, Maller ES, Yu C, Quan H, Simon T. Ulcer formation with low-dose enteric-coated aspirin and the effect of COX-2 selective inhibition: a double-blind trial. Gastroenterology. 2004 Aug;127(2):395-402. — View Citation

Lanas A, García-Rodríguez LA, Arroyo MT, Bujanda L, Gomollón F, Forné M, Aleman S, Nicolas D, Feu F, González-Pérez A, Borda A, Castro M, Poveda MJ, Arenas J; Investigators of the Asociación Española de Gastroenterología (AEG). Effect of antisecretory drugs and nitrates on the risk of ulcer bleeding associated with nonsteroidal anti-inflammatory drugs, antiplatelet agents, and anticoagulants. Am J Gastroenterol. 2007 Mar;102(3):507-15. — View Citation

Ma L, Elliott SN, Cirino G, Buret A, Ignarro LJ, Wallace JL. Platelets modulate gastric ulcer healing: role of endostatin and vascular endothelial growth factor release. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6470-5. Epub 2001 May 15. — View Citation

Mehta SR, Yusuf S, Peters RJ, Bertrand ME, Lewis BS, Natarajan MK, Malmberg K, Rupprecht H, Zhao F, Chrolavicius S, Copland I, Fox KA; Clopidogrel in Unstable angina to prevent Recurrent Events trial (CURE) Investigators. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet. 2001 Aug 18;358(9281):527-33. — View Citation

Ng FH, Wong SY, Chang CM, Chen WH, Kng C, Lanas AI, Wong BC. High incidence of clopidogrel-associated gastrointestinal bleeding in patients with previous peptic ulcer disease. Aliment Pharmacol Ther. 2003 Aug 15;18(4):443-9. — View Citation

Ng FH, Wong SY, Lam KF, Chu WM, Chan P, Ling YH, Kng C, Yuen WC, Lau YK, Kwan A, Wong BC. Famotidine is inferior to pantoprazole in preventing recurrence of aspirin-related peptic ulcers or erosions. Gastroenterology. 2010 Jan;138(1):82-8. doi: 10.1053/j.gastro.2009.09.063. Epub 2009 Nov 11. — View Citation

Norgard NB, Mathews KD, Wall GC. Drug-drug interaction between clopidogrel and the proton pump inhibitors. Ann Pharmacother. 2009 Jul;43(7):1266-74. doi: 10.1345/aph.1M051. Epub 2009 May 26. Review. — View Citation

Savi P, Nurden P, Nurden AT, Levy-Toledano S, Herbert JM. Clopidogrel: a review of its mechanism of action. Platelets. 1998;9(3-4):251-5. — View Citation

Sibbing D, Kastrati A. Risk of combining PPIs with thienopyridines: fact or fiction? Lancet. 2009 Sep 19;374(9694):952-954. doi: 10.1016/S0140-6736(09)61562-2. Epub 2009 Aug 31. — View Citation

Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Méneveau N, Steg PG, Ferrières J, Danchin N, Becquemont L; French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) Investigators. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med. 2009 Jan 22;360(4):363-75. doi: 10.1056/NEJMoa0808227. Epub 2008 Dec 22. — View Citation

Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK; Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001 Aug 16;345(7):494-502. Erratum in: N Engl J Med 2001 Dec 6;345(23):1716. N Engl J Med 2001 Nov 15;345(20):1506. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Ulcer Recurrence	Follow-up endoscopy was performed at the end of the 6th month	six month