## Protocol Section
### Identification Module
**NCT ID:** NCT06200779

**Brief Title:** Tailored vs. Empirical Helicobacter Pylori Infection Treatment

**Official Title:** Susceptibility-guided vs. Empirical First-line Bismuth Quadruple Therapy of H. Pylori Infection: a National Prospective Multicentric Randomized Controlled Trial.

#### Organization Study ID Info
**ID:** Clinical Study Protocol 1
#### Organization
**Class:** OTHER
**Full Name:** Unilabs Portugal
### Status Module
#### Completion Date
**Date:** 2025-11

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-08

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-07

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-06

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-09

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-01-11
**Type:** ACTUAL
**Study First Submit Date:** 2023-12-12
**Study First Submit QC Date:** 2023-12-30
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Manuel Coelho da Rocha

#### Responsible Party

**Investigator Affiliation:** Unilabs Portugal

**Investigator Full Name:** Manuel Coelho da Rocha

**Investigator Title:** Principal Investigator

**Type:** SPONSOR_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** Helicobacter pylori (Hp) is a gram-negative bacterium that colonizes human gastric mucosa and is associated with chronic gastritis that can progress to severe complications such as peptic ulcer disease, gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue lymphoma. More than half of the world's population is infected with H. pylori and Portugal is one of the countries with the highest Hp burden. All of infected patients should be treated, however, H. pylori treatment is challenged by the continuously rising antibiotic resistance which has reached alarming levels worldwide. For this reason, it is now well accepted that tailoring treatment of H. pylori infection based on systematic antimicrobial susceptibility testing is useful to avoid the increase of antibiotic resistance.

Our aims are to determine prospectively the efficacy and safety of first-line H. pylori eradication treatment based on resistance profile (determined by molecular methods) vs. empirical bismuth quadruple therapy, to evaluate the accuracy of H. pylori detection by polymerase chain reaction (PCR) (vs. histopathological examination) and to estimate the prevalence of H. pylori infection and H. pylori resistance to clarithromycin and levofloxacin in Portugal.

This prospective study will be the first national study to investigate the benefits of tailored H. pylori eradication treatment. The investigators expect that this project will be able to demonstrate the non-inferiority of susceptibility-guided treatment comparing with empirical therapy, and our results may change H. pylori treatment recommendations by systematically applying antibiotic susceptibility testing before prescribing eradication therapy.

**Detailed Description:** A prospective, multicenter, randomized, controlled interventional trial in two arms: intervention group and control group.

Eligible patients will receive oral and written information and will be enrolled after giving written informed consent.

In all patients complete gastroscopy with white light will be performed and endoscopic findings will be recorded. For each patient, gastric body and antral biopsies will be collected. All gastric samples will be tested for H. pylori infection by histopathological examination and PCR. All H. pylori positive samples will be tested for clarithromycin (mutations in the 23S rRNA gene, A2134G, A2142G and A2142C mutations) and levofloxacin resistance (mutations in the gyrA gene) by PCR.

All H. pylori positive patients will be randomized in two groups:

INTERVENTION GROUP: Patients randomized to the Intervention group will receive a prescription for oriented H. pylori eradication treatment according to the following rules: a) clarithromycin-sensitive strain (independently of levofloxacin resistance test result) - PPI, amoxicillin 1 g and clarithromycin 500 mg, twice daily, for 10 days; b) clarithromycin-resistant and levofloxacin-sensitive strain - PPI, amoxicillin 1g and levofloxacin 250 mg, twice daily, for 10 days; c) clarithromycin-resistant and levofloxacin-resistant strain - bismuth quadruple therapy (Pylera®) for 10 days. At least 4 weeks after stopping antibiotics (and at least 2 weeks after stopping PPIs), an eradication control test will be carried out using a respiratory test (urea breath test) or endoscopic biopsies (if clinical indication for that).

CONTROL GROUP: Patients randomized to the Control group will receive a prescription for empirically H. pylori eradication treatment with bismuth quadruple therapy (Pylera®) for 10 days. At least 4 weeks after stopping antibiotics (and at least 2 weeks after stopping PPIs), an eradication control test will be carried out using a respiratory test (urea breath test) or endoscopic biopsies (if clinical indication for that).

All patients that complete eradication treatment regimen will be evaluated 2 to 4 weeks after performing the eradication control (urea breath test) in a clinical consultation. Eventual adverse effects will be recorded. A negative breath test will define the success of the treatment, while a positive test will define treatment failure. The latter will be managed according to H. pylori infection guidelines.

### Conditions Module

**Conditions:**

- Helicobacter Pylori Infection

**Keywords:**

- Helicobacter pylori

- Antibiotic resistance

- Eradication treatment

- Molecular pathology

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** Intervention group: Patients will receive a prescription for oriented H. pylori eradication treatment according to the following rules: a) clarithromycin-sensitive strain (independently of levofloxacin resistance test result) - PPI, amoxicillin 1 g and clarithromycin 500 mg, twice daily, for 10 days; b) clarithromycin-resistant and levofloxacin-sensitive strain - PPI, amoxicillin 1g and levofloxacin 250 mg, twice daily, for 10 days; c) clarithromycin-resistant and levofloxacin-resistant strain - bismuth quadruple therapy (Pylera®) for 10 days.

Control Group: Patients will receive a prescription for empirically H. pylori eradication treatment with bismuth quadruple therapy (Pylera®) for 10 days.

##### Masking Info

**Masking:** SINGLE

**Who Masked:**

- INVESTIGATOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 160

**Type:** ESTIMATED

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Patients randomized to the Intervention group will receive a prescription for oriented H. pylori eradication treatment according to the following rules: a) clarithromycin-sensitive strain (independently of levofloxacin resistance test result) - PPI, amoxicillin 1 g and clarithromycin 500 mg, twice daily, for 10 days; b) clarithromycin-resistant and levofloxacin-sensitive strain - PPI, amoxicillin 1g and levofloxacin 250 mg, twice daily, for 10 days; c) clarithromycin-resistant and levofloxacin-resistant strain - bismuth quadruple therapy (Pylera®) for 10 days. At least 4 weeks after stopping antibiotics (and at least 2 weeks after stopping PPIs), an eradication control test will be carried out using a respiratory test (urea breath test) or endoscopic biopsies (if clinical indication for that).

**Intervention Names:**

- Diagnostic Test: Clarithromycin (mutations in the 23S rRNA gene, A2134G, A2142G and A2142C mutations) and levofloxacin resistance (mutations in the gyrA gene) PCR test

- Drug: PPI, amoxicillin 1 g and clarithromycin 500 mg, twice daily, for 10 days

- Drug: PPI, amoxicillin 1g and levofloxacin 250 mg, twice daily, for 10 days

- Drug: Bismuth quadruple therapy (Pylera®) for 10 days

**Label:** Intervention group

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** Patients randomized to the Control group will receive a prescription for empirically H. pylori eradication treatment with bismuth quadruple therapy (Pylera®) for 10 days. At least 4 weeks after stopping antibiotics (and at least 2 weeks after stopping PPIs), an eradication control test will be carried out using a respiratory test (urea breath test) or endoscopic biopsies (if clinical indication for that).

**Intervention Names:**

- Drug: Empirically H. pylori eradication treatment with bismuth quadruple therapy (Pylera®)

**Label:** Control group

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Intervention group

**Description:** Described in "Arms" section

**Name:** Clarithromycin (mutations in the 23S rRNA gene, A2134G, A2142G and A2142C mutations) and levofloxacin resistance (mutations in the gyrA gene) PCR test

**Type:** DIAGNOSTIC_TEST

#### Intervention 2

**Arm Group Labels:**

- Control group

**Description:** Described in "Arms" section

**Name:** Empirically H. pylori eradication treatment with bismuth quadruple therapy (Pylera®)

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Intervention group

**Description:** Administered to patients randomized to Intervention group and with H. pylori clarithromycin-sensitive strain

**Name:** PPI, amoxicillin 1 g and clarithromycin 500 mg, twice daily, for 10 days

**Type:** DRUG

#### Intervention 4

**Arm Group Labels:**

- Intervention group

**Description:** Administered to patients randomized to Intervention group and with H. pylori clarithromycin-resistant and levofloxacin-sensitive strain

**Name:** PPI, amoxicillin 1g and levofloxacin 250 mg, twice daily, for 10 days

**Type:** DRUG

#### Intervention 5

**Arm Group Labels:**

- Intervention group

**Description:** Administered to patients randomized to Intervention group and with H. pylori clarithromycin-resistant and levofloxacin-resistant strain

**Name:** Bismuth quadruple therapy (Pylera®) for 10 days

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** This comparation will allow the investigators to show the non-inferiority of susceptibility-guided treatment comparing with empirical therapy

**Measure:** Percentage of successful H. pylori eradication treatment in intervention group vs. control group.

**Time Frame:** 12 months

#### Secondary Outcomes

**Description:** All gastric samples will be tested for H. pylori infection by histopathological examination and PCR. This comparation will allow the investigators to analyze tha diagnostica accuracy of PCR vs. histopathological examination

**Measure:** Percentage of H. pylori detection in gastric samples by PCR vs. histopathological examination.

**Time Frame:** 12 months

**Measure:** Estimate the prevalence of H. pylori infection in Portugal.

**Time Frame:** 12 months

**Measure:** Estimate the prevalence of H. pylori resistance to clarithromycin and levofloxacin in Portugal.

**Time Frame:** 12 months

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Individuals older than 18 years old scheduled for upper GI endoscopy with indication for gastric biopsies (clinical or endoscopic findings)

Exclusion Criteria:

* 1st phase (clinical): patients who had received antimicrobial therapy 1 month prior to endoscopy; patients who had received proton pump inhibitor (PPI) therapy 2 weeks prior to endoscopy; patients who had ever received H. pylori eradication therapy (despite its efficacy); history of previous gastrectomy; non-Portuguese nationality; pregnant or breastfeeding women; women of childbearing age without effective contraception; suspected or documented allergy to amoxicillin; serious comorbidities (ASA 3 or more); ongoing medication with anticoagulants
* 2nd phase (endoscopic): upper GI tract neoplasia; hemorrhagic gastritis; upper GI tract varices
* 3rd phase (pathological): H. pylori negative patients

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Porto

**Contacts:**

***Contact 1:***

- **Email:** manuel.rocha@external.unilabs.com

- **Name:** Manuel Coelho da Rocha, MD

- **Phone:** +351964607421

- **Role:** CONTACT

***Contact 2:***

- **Email:** pedro.nunes@external.unilabs.com

- **Name:** Pedro Pimentel Nunes, MD PhD

- **Phone:** +351967340096

- **Role:** CONTACT

**Country:** Portugal

**Facility:** Unilabs Portugal

**Zip:** 4150-178

### IPD Sharing Statement Module

**Description:** All IPD that underlie results in a publication

**Info Types:**

- STUDY_PROTOCOL

- SAP

- ICF

- CSR

**IPD Sharing:** YES

**Time Frame:** Starting in May 2025

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020969

- Term: Disease Attributes

- ID: D000010335

- Term: Pathologic Processes

- ID: D000016905

- Term: Gram-Negative Bacterial Infections

- ID: D000001424

- Term: Bacterial Infections

- ID: D000001423

- Term: Bacterial Infections and Mycoses

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M10283

- Name: Infections

- Relevance: HIGH

- As Found: Infection

- ID: M6368

- Name: Communicable Diseases

- Relevance: HIGH

- As Found: Infection

- ID: M7380

- Name: Disease Susceptibility

- Relevance: LOW

- As Found: Unknown

- ID: M18886

- Name: Helicobacter Infections

- Relevance: HIGH

- As Found: Helicobacter Pylori Infection

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

- ID: M4722

- Name: Bacterial Infections

- Relevance: LOW

- As Found: Unknown

- ID: M19249

- Name: Gram-Negative Bacterial Infections

- Relevance: LOW

- As Found: Unknown

- ID: M12136

- Name: Mycoses

- Relevance: LOW

- As Found: Unknown

- ID: M4721

- Name: Bacterial Infections and Mycoses

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000007239

- Term: Infections

- ID: D000003141

- Term: Communicable Diseases

- ID: D000016481

- Term: Helicobacter Infections

### Intervention Browse Module - Ancestors

- ID: D000000900

- Term: Anti-Bacterial Agents

- ID: D000000890

- Term: Anti-Infective Agents

- ID: D000011500

- Term: Protein Synthesis Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000065692

- Term: Cytochrome P-450 CYP3A Inhibitors

- ID: D000065607

- Term: Cytochrome P-450 Enzyme Inhibitors

- ID: D000000892

- Term: Anti-Infective Agents, Urinary

- ID: D000059005

- Term: Topoisomerase II Inhibitors

- ID: D000059003

- Term: Topoisomerase Inhibitors

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000065609

- Term: Cytochrome P-450 CYP1A2 Inhibitors

- ID: D000000863

- Term: Antacids

- ID: D000005765

- Term: Gastrointestinal Agents

- ID: D000000981

- Term: Antiprotozoal Agents

- ID: D000000977

- Term: Antiparasitic Agents

- ID: D000000897

- Term: Anti-Ulcer Agents

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: Gast

- Name: Gastrointestinal Agents

### Intervention Browse Module - Browse Leaves

- ID: M16759

- Name: Tin Fluorides

- Relevance: LOW

- As Found: Unknown

- ID: M3995

- Name: Amoxicillin

- Relevance: HIGH

- As Found: Pembrolizumab

- ID: M4222

- Name: Anti-Bacterial Agents

- Relevance: LOW

- As Found: Unknown

- ID: M30370

- Name: Levofloxacin

- Relevance: HIGH

- As Found: Sodium chloride

- ID: M17946

- Name: Ofloxacin

- Relevance: HIGH

- As Found: Sodium chloride

- ID: M5011

- Name: Bismuth

- Relevance: HIGH

- As Found: Airway Pressure

- ID: M4224

- Name: Antibiotics, Antitubercular

- Relevance: LOW

- As Found: Unknown

- ID: M19585

- Name: Clarithromycin

- Relevance: HIGH

- As Found: Prescription

- ID: M1804

- Name: Carbamide Peroxide

- Relevance: LOW

- As Found: Unknown

- ID: M11767

- Name: Metronidazole

- Relevance: HIGH

- As Found: Scoliosis Surgery

- ID: M16520

- Name: Tetracycline

- Relevance: HIGH

- As Found: Scoliosis Surgery

- ID: M226511

- Name: Bismuth tripotassium dicitrate

- Relevance: HIGH

- As Found: Scoliosis Surgery

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M30564

- Name: Cytochrome P-450 CYP3A Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M30537

- Name: Cytochrome P-450 Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M4188

- Name: Antacids

- Relevance: LOW

- As Found: Unknown

- ID: M4219

- Name: Anti-Ulcer Agents

- Relevance: LOW

- As Found: Unknown

- ID: M8881

- Name: Gastrointestinal Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4298

- Name: Antiprotozoal Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4294

- Name: Antiparasitic Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000000658

- Term: Amoxicillin

- ID: D000017291

- Term: Clarithromycin

- ID: D000064704

- Term: Levofloxacin

- ID: D000015242

- Term: Ofloxacin

- ID: D000008795

- Term: Metronidazole

- ID: D000013752

- Term: Tetracycline

- ID: C000002791

- Term: Bismuth tripotassium dicitrate

- ID: D000001729

- Term: Bismuth

### Misc Info Module

- Version Holder: 2024-05-24
