RCT: Triple vs Sequential vs Concomitant Therapy H Pylori

NCT02092506 | Completed Phase 4 DMC

• 1 other identifier: 2011/389/E
• Study Type: interventional
• Target: 462
• Locations: 1 country
• Sites: 1

Brief Summary

Triple therapy (TT) comprising proton pump inhibitor (PPI), amoxicillin 1g and clarithromycin 500mg twice daily has long been considered one of the standard treatment for H. pylori infection as initial studies demonstrated success rates of \> 90% on per protocol analysis (PP) and \> 80% on intention to treat (ITT) analysis. However increasing bacterial resistance, especially to clarithromycin, has been reported and there are concerns that the efficacy of TT has decreased. Sequential therapy (ST) is an alternative first line therapy that consists of 5 days of treatment with a PPI and amoxicillin followed by 5-day treatment with the PPI and clarithromycin and metronidazole. The rationale for this approach is that amoxicillin may weaken the bacterial cell wall in the initial phase of treatment, and prevent the development of drug efflux channels that inhibit clarithromycin from binding to ribosomes and thus help to improve the efficacy of clarithromycin in the second phase of treatment. A recent meta-analysis based on mainly European studies showed that the success rate of ST compared to TT was 92.8 - 96% vs. 76.2 - 78.8%. Concomitant therapy (CT) is another alternative first line treatment that consists of 10 days of PPI, amoxicillin, clarithromycin and metronidazole. The rationale for using CT as a first line treatment option is to address the possibility of clarithromycin resistance which is increasingly encountered in clinical practice. Currently there are no randomized controlled studies that compared TT with ST in Singapore, although both regimens are being used in routine clinical practice. The hypothesis is that ST is superior to TT as first line treatment for H. pylori infection. The study aim to compare 10-day TT versus 10-day ST versus 10-day CT as first line treatment for H. pylori infection in Singapore.

Conditions

Bacterial Infection Due to Helicobacter Pylori (H. Pylori)

Keywords

H pylori; therapy

Outcome Measures

Primary Outcomes (1)

• H pylori eradication rate

  H pylori eradication rate

  at least 4 weeks up to 24 weeks after finishing course of antibiotics

Study Arms (3)

triple therapy

ACTIVE COMPARATOR

10 day triple therapy (PPI, amoxicillin 1g, clarithromycin 500mg twice daily)

Drug: 10 day triple therapy

Concomitant therapy

ACTIVE COMPARATOR

10-day concomitant therapy (PPI, amoxicillin 1g, clarithromycin 500mg, metronidazole 400mg twice daily).

Drug: 10 day sequential therapy

sequential therapy

ACTIVE COMPARATOR

10-day sequential therapy (PPI and amoxicillin 1 g twice daily x 5 days followed by PPI, clarithromycin 500mg, metronidazole 400mg twice daily x 5days)

Drug: 10 day concomitant therapy

Interventions

10 day triple therapy DRUG

10 day triple therapy

Also known as: Proton pump inhibitors bd, Amoxicillin 1 g bd, Clarithromycin 500mg bd

triple therapy

10 day sequential therapy DRUG

10 day sequential therapy

Also known as: Proton pump inhibitors bd, Amoxicillin 1g twice daily for 5 days, followed by clarithromycin 500mg bd for 5 days, Metronidazole 400mg bd for 5 days

Concomitant therapy

10 day concomitant therapy DRUG

10 day concomitant therapy

Also known as: Proton pump inhibitors bd, Amoxicillin 1 g bd, Clarithromycin 500 mg bd, Metronidazole 400 mg bd

sequential therapy

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• consecutive patients newly diagnosed to have H. pylori infection.

You may not qualify if:

• known allergy to any of the treatment drugs
• inability to undergo routine test to confirm success of H. pylori eradication
• previous H. pylori therapy.

Sponsors & Collaborators

• Changi General Hospital: lead

Study Sites (1)

Changi General Hospital

Singapore, Singapore, 529889, Singapore

Location

Related Publications (2)

• 1. Fock KM, Ang TL. Epidemiology of Helicobacter pylori infection and gastric cancer in Asia. J Gastroenterol Hepatol 2010;25:479-86. 2. Fock KM, Talley N, Moayyedi P et al. Asia-Pacific consensus guidelines on gastric cancer prevention. J Gastroenterol Hepatol 2008;23:351-65. 3. Fock KM, Katelaris P, Sugano K, et al. Second Asia-Pacific Conference. Second Asia-Pacific Consensus Guidelines for Helicobacter pylori infection. J Gastroenterol Hepatol 2009;24:1587-600. 4. Malfertheiner P, Megraud F, O'Morain C et al. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut 2007;56:772-81. 5. Malfertheiner P, Bayerdörffer E, Diete U et al. The GU-MACH study: the effect of 1-week omeprazole triple therapy on Helicobacter pylori infection in patients with gastric ulcer. Aliment. Pharmacol Ther 1999;13:703-12. 6. Zanten SJ, Bradette M, Farley A et al. The DU-MACH study: eradication of Helicobacter pylori and ulcer healing in patients with acute duodenal ulcer using omeprazole based triple therapy. Aliment. Pharmacol Ther 1999;13:289-95. 7. Fock KM, Chelvam P, Lim SG. Triple therapy in the eradication of Helicobacter pylori in patients with duodenal ulcer disease: results of a multicentre study in South-East Asia. South-East Asia Multicenter Study Group. Aliment. Pharmacol. Ther. 2000;14:225-31. 8. Gatta L, Vakil N, Leandro G, Di Mario F, Vaira D. Sequential therapy or triple therapy for Helicobacter pylori infection: systematic review and meta-analysis of randomized controlled trials in adults and children. Am J Gastroenterol 2009;104:3069-79. 9. Rimbara E, Fischbach LA, Graham DY. Optimal therapy for Helicobacter pylori infections. Nat Rev Gastroenterol Hepatol 2011;8:79-88.

  BACKGROUND

• Ang TL, Fock KM, Song M, Ang D, Kwek AB, Ong J, Tan J, Teo EK, Dhamodaran S. Ten-day triple therapy versus sequential therapy versus concomitant therapy as first-line treatment for Helicobacter pylori infection. J Gastroenterol Hepatol. 2015 Jul;30(7):1134-9. doi: 10.1111/jgh.12892.

  PMID: 25639278 DERIVED

MeSH Terms

Interventions

Amoxicillin; Clarithromycin; Metronidazole

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Tiing Leong Ang, MD

  Changi General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2014
• First Posted: March 20, 2014
• Study Start: December 1, 2011
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: July 8, 2014

Record last verified: 2014-07

Locations

SG (1)