HELicobacter Pylori Screening to Prevent Gastrointestinal Bleeding in Patients With Acute Myocardial Infarction

NCT05024864 | Active Not Recruiting

• 1 other identifier: HELP-MI SWEDEHEART
• Study Type: interventional
• Target: 20,000
• Locations: 1 country
• Sites: 35

Brief Summary

Background: Potent antithrombotic therapy has improved prognosis for patients with acute myocardial infarction (MI) significantly, however, at a price of increased bleeding risk. Helicobacter pylori (H. pylori) infection commonly causes upper gastrointestinal bleeding (UGIB). If systematic screening for H. pylori significantly reduces the risk of UGIB and improves outcomes is unknown. Study design: A cluster randomized, cross-over, registry-based clinical trial using nationwide Swedish registries for study population definition and data collection. Population: Patients discharged alive after hospitalization for acute type 1 MI at up to 40 hospitals across Sweden. Regional PCI networks comprise 18 clusters. Clusters will be randomized to routine H. pylori screening or no screening for 1 year after which cross-over to the opposite strategy occurs for 1 year. The study ends after one additional year of registry-based follow-up, one year after the end of the second period. Intervention: All MI patients will routinely be offered screening for H. pylori by urea breath test. Controls: Standard clinical practice. Data will be collected from SWEDEHEART and national registries. For patients testing H. pylori positive, eradication therapy will be prescribed at the caring physician's discretion. The individual implementation of H. pylori screening, test result and eradication therapy prescription will be recorded in SWEDEHEART. All follow-up data is collected from SWEDEHEART and national registries. Outcome: Primary outcome is UGIB defined as hospitalization or an outpatient visit in specialized care with ICD codes corresponding to UGIB. The secondary endpoints (in hierarchical) order:

1. 1.Net Adverse Clinical Events (NACE): All-cause death, UGIB, hospitalization for MI, or hospitalization for ischemic stroke.
2. 2.Major Adverse Cardiovascular and Cerebrovascular Events (MACCE): CV death, hospitalization for MI, or hospitalization for ischemic stroke.
3. 3.All-cause death.
4. 4.CV death.
5. 5.Hospitalization for MI.
6. 6.Hospitalization for stroke.
7. 7.Hospitalization for HF.
8. 8.UGIB requiring blood transfusion.

Conditions

Myocardial Infarction; Helicobacter Pylori Infection; GastroIntestinal Bleeding; Cardiovascular Diseases

Keywords

Myocardial infarction; Helicobacter Pylori Infection; GastroIntestinal Bleeding; Cardiovascular Diseases; Registry based randomized clinical trial; Mortality; Cluster-randomized crossover trial

Outcome Measures

Primary Outcomes (1)

• Upper gastrointestinal bleeding (UGIB)

  Time from discharge date of index MI hospitalization to UGIB

  Time from discharge date of index MI hospitalization to the end of study follow-up, January 17, 2025 (corresponds to a maximum follow-up time of 3 years and 2 months, and minimum of 1 year).

Secondary Outcomes (8)

• Net Adverse Clinical Events (NACE)

  Time from discharge date of index MI hospitalization to the end of study follow-up, January 17, 2025 (corresponds to a maximum follow-up time of 3 years and 2 months, and minimum of 1 year).

• Major Adverse Cardiac or Cerebrovascular Events (MACCE)

  Time from discharge date of index MI hospitalization to the end of study follow-up, January 17, 2025 (corresponds to a maximum follow-up time of 3 years and 2 months, and minimum of 1 year).

• All-cause death

  Time from discharge date of index MI hospitalization to the end of study follow-up, January 17, 2025 (corresponds to a maximum follow-up time of 3 years and 2 months, and minimum of 1 year).

• Cardiovascular death

  Time from discharge date of index MI hospitalization to the end of study follow-up, January 17, 2025 (corresponds to a maximum follow-up time of 3 years and 2 months, and minimum of 1 year).

• Rehospitalization with myocardial infarction

  Time from discharge date of index MI hospitalization to the end of study follow-up, January 17, 2025 (corresponds to a maximum follow-up time of 3 years and 2 months, and minimum of 1 year).

Other Outcomes (10)

• CCS

  6-10 weeks after discharge date of index MI hospitalization

• CCS

  11-13 months after discharge date of index MI hospitalization

• NYHA

  6-10 weeks after discharge date of index MI hospitalization

Study Arms (2)

Helicobacter pylori screening

ACTIVE COMPARATOR

At centers randomized to screening, all patients with confirmed MI will be offered H. pylori screening with a bedside UBT incorporated into MI routine care during the hospitalization period. All H. pylori analysis equipment will be supplied by the study organizers, and all centers will use the same equipment (Kibion® Diabact®, Mayoly Spindler, Chatou, France). For patients testing H. pylori positive, eradication therapy will be prescribed at the caring physician's discretion. Control of successful H. pylori eradication therapy with either UBT or H. pylori-antigen in feces 6 weeks after completed eradication therapy will be recommended to the treating physician but not centrally followed-up. The individual implementation of H. pylori screening, test result and eradication therapy prescription will be recorded in SWEDEHEART.

Diagnostic Test: Urea breath test (UBT)

Usual care without Helicobacter pylori screening

NO INTERVENTION

At centers randomized to no screening, all MI patients will receive usual care and will be followed in SWEDEHEART and national registries.

Interventions

Urea breath test (UBT) DIAGNOSTIC_TEST

After fasting for six hours prior to testing, the patient swallows a C13 Urea tablet or solution and waits. After 10 minutes, the patient exhales and breath is collected (breath bag). The production of 13CO2 is measured by a desktop analyzer (infrared mass spectrometry) and active H. pylori infection diagnosis is made based on previously established cut-off levels for H. pylori infection. In patients tested positive, eradication therapy according to the national society of gastroenterology guidelines will be prescribed at the caring physician's discretion. Control of successful H. pylori eradication 6 weeks after completed eradication therapy is recommended to the treating physician. During the period without H. pylori screening, the study´s UBT equipment will not be available.

Helicobacter pylori screening

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18
• Registered in SWEDEHEART as discharged alive at a study site with a diagnosis of type 1 MI (including ICD-10 code I21 or I22).

You may not qualify if:

• None

Sponsors & Collaborators

• Karolinska Institutet: lead
• Region Stockholm: collaborator
• The Swedish Research Council: collaborator
• Hjärt-Lungfonden, Sweden: collaborator

Study Sites (35)

Södra Älvsborg Hospital

Borås, Sweden

Location

Eskilstuna Hospital

Eskilstuna, Sweden

Location

Falun Hospital

Falun, Sweden

Location

Gävle Hospital

Gävle, Sweden

Location

Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Östra Hospital

Gothenburg, Sweden

Location

Halmstad Hospital

Halmstad, Sweden

Location

Helsingborg Hospital

Helsingborg, Sweden

Location

Ryhov Hospital

Jönköping, Sweden

Location

Karlskrona Hospital

Karlskrona, Sweden

Location

Köping Hospital

Köping, Sweden

Location

Kristianstad Hospital

Kristianstad, Sweden

Location

Kungälv Hospital

Kungälv, Sweden

Location

Lidköping Hospital

Lidköping, Sweden

Location

Linköping University Hospital

Linköping, Sweden

Location

Skåne University Hospital Lund

Lund, Sweden

Location

Skåne University Hospital Malmö

Malmo, Sweden

Location

Mora Hospital

Mora, Sweden

Location

Motala Hospital

Motala, Sweden

Location

Mölndal Hospital

Mölndal, Sweden

Location

Vrinnevisjukhuset

Norrköping, Sweden

Location

Norrtälje Hospital

Norrtälje, Sweden

Location

Nyköping Hospital

Nyköping, Sweden

Location

Örebro University Hospital

Örebro, Sweden

Location

Sunderby Hospital

Södra Sunderbyn, Sweden

Location

Danderyds University Hospital

Stockholm, Sweden

Location

Karolinska University Hospital Huddinge

Stockholm, Sweden

Location

Karolinska University Hospital Solna

Stockholm, Sweden

Location

Sankt Görans Hospital

Stockholm, Sweden

Location

Södersjukhuset

Stockholm, Sweden

Location

Norra Älvsborgs Länssjukhus

Trollhättan, Sweden

Location

Norrland University Hospital

Umeå, Sweden

Location

Uppsala University Hospital

Uppsala, Sweden

Location

Varberg Hospital

Varberg, Sweden

Location

Västerås Hospital

Västerås, Sweden

Location

Related Publications (22)

• Hofmann R, Back M. Time for Routine Helicobacter pylori Screening in Coronary Artery Disease? Circulation. 2023 Jun 6;147(23):1731-1733. doi: 10.1161/CIRCULATIONAHA.123.064944. Epub 2023 Jun 5. No abstract available.

  PMID: 37276250 BACKGROUND

• Sundqvist MO, Warme J, Hofmann R, Pawelzik SC, Back M. Helicobacter Pylori Virulence Factor Cytotoxin-Associated Gene A (CagA) Induces Vascular Calcification in Coronary Artery Smooth Muscle Cells. Int J Mol Sci. 2023 Mar 11;24(6):5392. doi: 10.3390/ijms24065392.

  PMID: 36982467 BACKGROUND

• Warme J, Sundqvist MO, James S, Hofmann R. Screening for Helicobacter pylori infection in patients with cardiovascular and gastrointestinal disease. Nat Rev Cardiol. 2024 Aug;21(8):593. doi: 10.1038/s41569-024-01028-8. No abstract available.

  PMID: 38698181 BACKGROUND

• Capodanno D, Bhatt DL, Gibson CM, James S, Kimura T, Mehran R, Rao SV, Steg PG, Urban P, Valgimigli M, Windecker S, Angiolillo DJ. Bleeding avoidance strategies in percutaneous coronary intervention. Nat Rev Cardiol. 2022 Feb;19(2):117-132. doi: 10.1038/s41569-021-00598-1. Epub 2021 Aug 23.

  PMID: 34426673 BACKGROUND

• Lanas A, Santilli F. Aspirin and Helicobacter pylori interaction. Lancet. 2022 Nov 5;400(10363):1560-1561. doi: 10.1016/S0140-6736(22)02000-1. No abstract available.

  PMID: 36335960 BACKGROUND

• Hawkey C, Avery A, Coupland CAC, Crooks C, Dumbleton J, Hobbs FDR, Kendrick D, Moore M, Morris C, Rubin G, Smith M, Stevenson D; HEAT Trialists. Helicobacter pylori eradication for primary prevention of peptic ulcer bleeding in older patients prescribed aspirin in primary care (HEAT): a randomised, double-blind, placebo-controlled trial. Lancet. 2022 Nov 5;400(10363):1597-1606. doi: 10.1016/S0140-6736(22)01843-8.

  PMID: 36335970 BACKGROUND

• Mascellino MT, Pontone S, Vega AE, Malfertheiner P. Editorial: Helicobacter pylori infection: pathogenesis, antibiotic resistance, advances and therapy, new treatment strategies. Front Microbiol. 2022 Dec 8;13:1102144. doi: 10.3389/fmicb.2022.1102144. eCollection 2022. No abstract available.

  PMID: 36569072 BACKGROUND

• Malfertheiner P, Megraud F, Rokkas T, Gisbert JP, Liou JM, Schulz C, Gasbarrini A, Hunt RH, Leja M, O'Morain C, Rugge M, Suerbaum S, Tilg H, Sugano K, El-Omar EM; European Helicobacter and Microbiota Study group. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022 Aug 8:gutjnl-2022-327745. doi: 10.1136/gutjnl-2022-327745. Online ahead of print.

  PMID: 35944925 BACKGROUND

• Talasaz AH, Sadeghipour P, Ortega-Paz L, Kakavand H, Aghakouchakzadeh M, Beavers C, Fanikos J, Eikelboom JW, Siegal DM, Monreal M, Jimenez D, Vaduganathan M, Castellucci LA, Cuker A, Barnes GD, Connors JM, Secemsky EA, Van Tassell BW, De Caterina R, Kurlander JE, Aminian A, Piazza G, Goldhaber SZ, Moores L, Middeldorp S, Kirtane AJ, Elkind MSV, Angiolillo DJ, Konstantinides S, Lip GYH, Stone GW, Cushman M, Krumholz HM, Mehran R, Bhatt DL, Bikdeli B. Optimizing antithrombotic therapy in patients with coexisting cardiovascular and gastrointestinal disease. Nat Rev Cardiol. 2024 Aug;21(8):574-592. doi: 10.1038/s41569-024-01003-3. Epub 2024 Mar 20.

  PMID: 38509244 BACKGROUND

• Sarri GL, Grigg SE, Yeomans ND. Helicobacter pylori and low-dose aspirin ulcer risk: A meta-analysis. J Gastroenterol Hepatol. 2019 Mar;34(3):517-525. doi: 10.1111/jgh.14539. Epub 2018 Dec 17.

  PMID: 30408229 BACKGROUND

• Malfertheiner P, Megraud F, O'Morain CA, Gisbert JP, Kuipers EJ, Axon AT, Bazzoli F, Gasbarrini A, Atherton J, Graham DY, Hunt R, Moayyedi P, Rokkas T, Rugge M, Selgrad M, Suerbaum S, Sugano K, El-Omar EM; European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut. 2017 Jan;66(1):6-30. doi: 10.1136/gutjnl-2016-312288. Epub 2016 Oct 5.

  PMID: 27707777 BACKGROUND

• Lindholm D, Sarno G, Erlinge D, Svennblad B, Hasvold LP, Janzon M, Jernberg T, James SK. Combined association of key risk factors on ischaemic outcomes and bleeding in patients with myocardial infarction. Heart. 2019 Aug;105(15):1175-1181. doi: 10.1136/heartjnl-2018-314590. Epub 2019 May 4.

  PMID: 31055499 BACKGROUND

• Eikelboom JW, Connolly SJ, Bosch J, Shestakovska O, Aboyans V, Alings M, Anand SS, Avezum A, Berkowitz SD, Bhatt DL, Cook-Bruns N, Felix C, Fox KAA, Hart RG, Maggioni AP, Moayyedi P, O'Donnell M, Ryden L, Verhamme P, Widimsky P, Zhu J, Yusuf S. Bleeding and New Cancer Diagnosis in Patients With Atherosclerosis. Circulation. 2019 Oct 29;140(18):1451-1459. doi: 10.1161/CIRCULATIONAHA.119.041949. Epub 2019 Sep 12.

  PMID: 31510769 BACKGROUND

• Fang Y, Fan C, Xie H. Effect of Helicobacter pylori infection on the risk of acute coronary syndrome: A systematic review and meta-analysis. Medicine (Baltimore). 2019 Dec;98(50):e18348. doi: 10.1097/MD.0000000000018348.

  PMID: 31852134 BACKGROUND

• Ng JC, Yeomans ND. <em>Helicobacter pylori</em> infection and the risk of upper gastrointestinal bleeding in low dose aspirin users: systematic review and meta-analysis. Med J Aust. 2018 Sep 1;209(7):306-311. doi: 10.5694/mja17.01274.

  PMID: 30257623 BACKGROUND

• Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017 Feb;112(2):212-239. doi: 10.1038/ajg.2016.563. Epub 2017 Jan 10.

  PMID: 28071659 BACKGROUND

• Xu Z, Li J, Wang H, Xu G. Helicobacter pylori infection and atherosclerosis: is there a causal relationship? Eur J Clin Microbiol Infect Dis. 2017 Dec;36(12):2293-2301. doi: 10.1007/s10096-017-3054-0. Epub 2017 Jul 27.

  PMID: 28752210 BACKGROUND

• Warme J, Sundqvist M, Mars K, Aladellie L, Pawelzik SC, Erlinge D, Jernberg T, James S, Hofmann R, Back M. Helicobacter pylori screening in clinical routine during hospitalization for acute myocardial infarction. Am Heart J. 2021 Jan;231:105-109. doi: 10.1016/j.ahj.2020.10.072. Epub 2020 Nov 2.

  PMID: 33144087 BACKGROUND

• Hellstrom PM, Benno P, Malfertheiner P. Gastrointestinal bleeding in patients with Helicobacter pylori and dual platelet inhibition after myocardial infarction. Lancet Gastroenterol Hepatol. 2021 Sep;6(9):684-685. doi: 10.1016/S2468-1253(21)00192-8. No abstract available.

  PMID: 34391514 BACKGROUND

• Sarajlic P, Simonsson M, Jernberg T, Back M, Hofmann R. Incidence, associated outcomes, and predictors of upper gastrointestinal bleeding following acute myocardial infarction: a SWEDEHEART-based nationwide cohort study. Eur Heart J Cardiovasc Pharmacother. 2022 Aug 11;8(5):483-491. doi: 10.1093/ehjcvp/pvab059.

  PMID: 34423350 BACKGROUND

• Hofmann R, James S, Sundqvist MO, Warme J, Angeras O, Alfredsson J, Erlinge D, Arefalk G, Arstad G, Blomberg S, Frobert O, Hambraeus K, Hellstrom PM, Lauermann J, Lidin M, Lindhagen L, Mourtzinis G, Schoede C, Thunstrom E, Voldberg B, Wagner H, Ostlund O, Jernberg T, Back M. Helicobacter pylori Screening After Acute Myocardial Infarction: The Cluster Randomized Crossover HELP-MI SWEDEHEART Trial. JAMA. 2025 Oct 7;334(13):1160-1169. doi: 10.1001/jama.2025.15047.

  PMID: 40887995 DERIVED

• Hofmann R, James S, Sundqvist MO, Warme J, Frobert O, Angeras O, Hellstrom PM, Hambraeus K, Alfredsson J, Erlinge D, Lauermann J, Lindhagen L, Ostlund O, Jernberg T, Back M. HELicobacter Pylori screening to prevent gastrointestinal bleeding in patients with acute Myocardial Infarction (HELP-MI SWEDEHEART) - Design and rationale of a cluster randomized, crossover, registry-based clinical trial. Am Heart J. 2025 Aug;286:66-74. doi: 10.1016/j.ahj.2025.03.014. Epub 2025 Mar 27.

  PMID: 40157409 DERIVED

MeSH Terms

Conditions

Myocardial Infarction; Gastrointestinal Hemorrhage; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Gastrointestinal Diseases; Digestive System Diseases; Hemorrhage

Study Officials

• Robin Hofmann, MD, PhD

  Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset, Stockholm.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcomes assessors will be blinded to randomized cluster assignment of screening/observation period.
• Purpose: SCREENING
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: Cluster-randomized, crossover, registry-based clinical trial

Study Record Dates

• First Submitted: August 23, 2021
• First Posted: August 27, 2021
• Study Start: November 17, 2021
• Primary Completion: January 17, 2025
• Study Completion (Estimated): January 17, 2030
• Last Updated: June 19, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

SE (35)