Study to Evaluate the Performance and Safety of the MARIAL® in Association With PPI Versus PPI Alone

NCT04130659 | Unknown

• 2 other identifiers: NEK/MD/01192019-004062-17
• Study Type: interventional
• Target: 110
• Locations: 2 countries
• Sites: 5

Brief Summary

Many patients with acid reflux disease do not improve with regular doses of proton pump inhibitors (e.g., omeprazole). The goals of this clinical trial is the to see if taking MARIAL®, in combination with omeprazole, for one month improves symptoms of acid reflux disease compared to taking omeprazole alone. Furthermore, this study will verify the effectiveness of MARIAL® as a maintenance treatment for the next five months. This trial is called by the registered name GENYAL®.

Conditions

Gastroesophageal Reflux Disease (GERD)

Keywords

Medical Device; Proton-pump inhibitor; Gastroesophageal Reflux Disease; Magnesium Alginate; Mucosal protective agent

Outcome Measures

Primary Outcomes (1)

• Total Gaviscon® tablets consumption by patients using alginate as rescue medication

  The 28-day visit will assess the outcome by reviewing the patients' diary card. This diary card records their usage of Gaviscon® tablets and calculates the number of unused Gaviscon® tablets they received during baseline. The consumption of Gaviscon® tablets from baseline to the final visit in the Marial® + PPI group will be compared to that of the PPI-only group.

  28 days

Secondary Outcomes (8)

• Reflux Symptoms Index (RSI)

  180 days

• GERD Impact Scale (GIS)

  180 days

• GERD Health-Related Quality of Life (GERD-HRQL)

  180 days

• Investigator Global Assessment of the Performance (IGAP)

  180 days

• Investigator Global Assessment of Safety (IGAS)

  180 days

Study Arms (2)

MARIAL® and PPI; Follow-up period: MARIAL® alone

EXPERIMENTAL

Period 1, open comparative phase: MARIAL® and PPI administered from day 1 to day 28. Period 2, open non comparative follow up: MARIAL® alone administered from day 29 to month 6.

Combination Product: MARIAL® + PPI (generic Omeprazole); Device: MARIAL® alone

PPI alone; Follow-up period: MARIAL® alone

ACTIVE COMPARATOR

Period 1, open comparative phase: PPI alone administered from day 1 to day 28. Period 2, open non comparative follow up: MARIAL® alone administered from day 29 to month 6.

Drug: PPI alone (generic omeprazole); Device: MARIAL® alone

Interventions

MARIAL® + PPI (generic Omeprazole) COMBINATION_PRODUCT

MARIAL® administration: 1 stick twice daily after meals from day 1 to 28. Omeprazole administration: 20 mg cps once daily from day 1 to day 28

MARIAL® and PPI; Follow-up period: MARIAL® alone

PPI alone (generic omeprazole) DRUG

Omeprazole administration: 20 mg cps once daily from day 1 to day 28

PPI alone; Follow-up period: MARIAL® alone

MARIAL® alone DEVICE

MARIAL® administration: 1 stick twice daily after meals from day 29 to month 6.

MARIAL® and PPI; Follow-up period: MARIAL® alone; PPI alone; Follow-up period: MARIAL® alone

Eligibility Criteria

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

You may qualify if:

• Male or non-pregnant female, both aged ≥ 18 to ≤ 65 years.
• Diagnosis of GERD Grade A esophagitis on Los Angeles Classification System grades reflux esophagitis by:
• gastroscopy (done within 1-month prior baseline).
• episodic heartburn and/or acid regurgitation (at least 3 times per week in the last 2 weeks);
• Body mass index of ≥ 18.5 to ≤ 36 kg/m2.
• Able to communicate adequately with the investigator and to comply with the requirements for the entire study.
• Capable of and freely willing to provide written informed consent prior to participating in the study.

You may not qualify if:

• Intake of PPI or Marial® during the last 28 days before the start of the study.
• Intake of systemic glucocorticoids or non-steroidal anti-inflammatory drugs (NSAIDs) including COX-2-inhibitors (≥ 3 consecutive days per week) during the last 28 days before the start of the study; except regular intake of enteric coated aspirin dosages up to 150 mg/d.
• Previously underwent acid-lowering surgery or other surgery of the oesophagus and/or upper gastrointestinal tract (excluding appendectomy, cholecystectomy and polypectomy).
• History of co-existing disease that affects the esophagus (e.g. Barrett's esophagus, Zollinger-Ellison syndrome, esophageal stricture).
• History of active gastric or duodenal ulcers within 3 months of the first dose of the study drug or had acute upper gastrointestinal (GI) bleeding within last 6 months.
• Documented presence of severe renal or hepatic insufficiency (i.e. GOT, GPT elevated over double the normal range).
• Known hypersensitivity to omeprazole, and/or Marial® and/or Gaviscon®.
• Concurrent (or within 30 days of study entry) participation in a clinical trial.
• Females who are pregnant, or planning a pregnancy, or lactating. Females of child bearing potential not using reliable methods of birth control.
• Clinically significant laboratory abnormality or disease which, in the opinion of the Investigator, will create a risk for the patient, or interfere with study results (i.e. GOT, GPT elevated over double the normal range).
• Receiving any of the following drugs within 2 weeks before the baseline: theophylline, bismuth salts, warfarin, phenytoin, tacrolimus, diazepam, cyclosporine, disulfiram, barbiturates, antineoplastic agents, erythromycin, clarithromycin, sucralfate, clopidogrel or protease inhibitors. Benzodiazepines could be allowed only in concomitance with the endoscopy.
• Taking concomitant medications that rely on the presence of gastric acid for optimal bioavailability (e.g. ketoconazole, ampicillin esters or iron salts).
• Drug or alcohol abuse within 12 months of Day 0
• Malignancy (also leukemic infiltrates) within 5 years prior to Day 0 (except for treated basal cell/squamous cell carcinoma of the skin).
• Psychosis, schizophrenia, mania, depressive disorders, history of suicide attempt or suicidal ideation, or any other psychiatric illness (except for intermittent anxiety).

Sponsors & Collaborators

• Nekkar Lab Srl: lead
• Opera CRO, a TIGERMED Group Company: collaborator

Study Sites (5)

UOC Endoscopia Digestiva Chirurgica Policlinico Gemelli - Universita Cattolica

Roma, 00168, Italy

RECRUITING

Cabinet Particular Policlinic Algomed

Timișoara, Timiș County, 300002, Romania

COMPLETED

Societatea Civilă Medicală Gados

Timișoara, 300209, Romania

COMPLETED

Medlife SA

Timișoara, 300551, Romania

COMPLETED

Centrul Medical Salvosan Ciobanca

Zalău, 45051, Romania

COMPLETED

Related Publications (11)

• El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2014 Jun;63(6):871-80. doi: 10.1136/gutjnl-2012-304269. Epub 2013 Jul 13.

  PMID: 23853213 BACKGROUND

• Kung YM, Hsu WH, Wu MC, Wang JW, Liu CJ, Su YC, Kuo CH, Kuo FC, Wu DC, Wang YK. Recent Advances in the Pharmacological Management of Gastroesophageal Reflux Disease. Dig Dis Sci. 2017 Dec;62(12):3298-3316. doi: 10.1007/s10620-017-4830-5. Epub 2017 Nov 6.

  PMID: 29110162 BACKGROUND

• Strugala V, Avis J, Jolliffe IG, Johnstone LM, Dettmar PW. The role of an alginate suspension on pepsin and bile acids - key aggressors in the gastric refluxate. Does this have implications for the treatment of gastro-oesophageal reflux disease? J Pharm Pharmacol. 2009 Aug;61(8):1021-8. doi: 10.1211/jpp/61.08.0005.

  PMID: 19703345 BACKGROUND

• Aragona SE, Mereghetti G, Bianchetti M, Mangiavillano B, Zurlo T, Lotti J, La Mantia I, Franca K, Lotti T. Regenerative medicine in the treatment of gastro-esophageal reflux disease and laryngo-pharyngeal reflux. From research to cure. J Biol Regul Homeost Agents. 2017 APR-JUN;31(2 Suppl. 2):207-212.

  PMID: 28702984 BACKGROUND

• DeVault K, McMahon BP, Celebi A, Costamagna G, Marchese M, Clarke JO, Hejazi RA, McCallum RW, Savarino V, Zentilin P, Savarino E, Thomson M, Souza RF, Donohoe CL, O'Farrell NJ, Reynolds JV. Defining esophageal landmarks, gastroesophageal reflux disease, and Barrett's esophagus. Ann N Y Acad Sci. 2013 Oct;1300:278-295. doi: 10.1111/nyas.12253.

  PMID: 24117649 BACKGROUND

• Aragona SE, Mereghetti G, Ciprandi G. Gastric reflux: the therapeutical role of Marial(R). J Biol Regul Homeost Agents. 2018 Jul-Aug;32(4):969-972.

  PMID: 29687692 BACKGROUND

• Hillman L, Yadlapati R, Thuluvath AJ, Berendsen MA, Pandolfino JE. A review of medical therapy for proton pump inhibitor nonresponsive gastroesophageal reflux disease. Dis Esophagus. 2017 Sep 1;30(9):1-15. doi: 10.1093/dote/dox055.

  PMID: 28859358 BACKGROUND

• Reimer C, Lodrup AB, Smith G, Wilkinson J, Bytzer P. Randomised clinical trial: alginate (Gaviscon Advance) vs. placebo as add-on therapy in reflux patients with inadequate response to a once daily proton pump inhibitor. Aliment Pharmacol Ther. 2016 Apr;43(8):899-909. doi: 10.1111/apt.13567. Epub 2016 Feb 22.

  PMID: 26909885 BACKGROUND

• Belafsky PC, Postma GN, Koufman JA. Validity and reliability of the reflux symptom index (RSI). J Voice. 2002 Jun;16(2):274-7. doi: 10.1016/s0892-1997(02)00097-8.

  PMID: 12150380 BACKGROUND

• Jones R, Coyne K, Wiklund I. The gastro-oesophageal reflux disease impact scale: a patient management tool for primary care. Aliment Pharmacol Ther. 2007 Jun 15;25(12):1451-9. doi: 10.1111/j.1365-2036.2007.03343.x.

  PMID: 17539985 BACKGROUND

• Spada C, Salvi D, Pecere S, Mangiola F, Varca S, Rosu S, Prateek V, Ciobanca PV, Goldis A, Barattini DF, Costamagna G. E-Gastryal(R) + Magnesium Alginate Plus PPI vs. PPI Alone in GERD: Results from the GENYAL(R) Randomized Controlled Trial. J Clin Med. 2025 Jul 7;14(13):4794. doi: 10.3390/jcm14134794.

  PMID: 40649167 DERIVED

MeSH Terms

Conditions

Gastroesophageal Reflux

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Officials

• Doina Rosu

  Societatea Civilă Medicală Gados

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Barattini Dionisio Franco

CONTACT

+39 3355437574; barattini@operacro.com

Dogaru Dumitru-Emanuel

CONTACT

+40 724345115; dogaru@operacro.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Neither the patients nor the Investigator will be blinded to the treatment to which the patients will be allocated.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, open-label, comparative, multicenter trial with two parallel groups of patients. At the end of the 28-day (± 1) 1st study period, patients will be included in an open-label, non-comparative follow-up (2nd study period) and treated with MARIAL® for additional 5 months from baseline.

Study Record Dates

• First Submitted: October 14, 2019
• First Posted: October 17, 2019
• Study Start: August 8, 2019
• Primary Completion: December 31, 2024
• Study Completion: January 31, 2025
• Last Updated: December 15, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

RO (4); IT (1)