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

NCT ID: NCT04130659

Last Updated: 2023-12-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

110 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-08

Study Completion Date

2025-01-31

Brief Summary

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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®.

Detailed Description

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This is an open-label, comparative, multicenter study with two parallel groups of patients. The clinical trial has the registered name GENYAL® and will be conducted at five clinical sites.

The study population will include patients affected by gastroesophageal reflux disease (GERD) with a diagnosis of Los Angeles Classification System Grade A reflux esophagitis confirmed by gastroscopy (performed within 1 month prior to baseline) and clinical symptoms in the past 2 weeks.

Patients will be randomized to receive MARIAL® (E-Gastryal®+Magnesium Alginate) plus omeprazole versus omeprazole alone (1 month) followed by Marial® alone for an additional 5 months. The products will be administered following the respective Summary of Product Characteristics. The Investigators chosen the number of rescue medicine used (tablets of Gaviscon®) as a primary efficacy outcome to measure the performance between the two groups. The study will enroll 110 patients.

MARIAL® is a class IIa medical device that is already marketed in several EU countries. It is a combination of E-Gastryal® (hyaluronic acid, hydrolyzed keratin, tara gum, xantan gum, purified water) and magnesium alginate (MgAlg). It has been proven to actively regenerate damaged tissues through its repair and regenerative properties on the mucous membranes and its mucoadhesive and film-forming properties, which prolong the contact time with the mucous membranes and consequently improve their effectiveness.

Conditions

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Gastroesophageal Reflux Disease (GERD)

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Neither the patients nor the Investigator will be blinded to the treatment to which the patients will be allocated.

Study Groups

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

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.

Group Type EXPERIMENTAL

MARIAL® + PPI (generic Omeprazole)

Intervention Type 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® alone

Intervention Type DEVICE

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

PPI alone; Follow-up period: MARIAL® alone

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.

Group Type ACTIVE_COMPARATOR

PPI alone (generic omeprazole)

Intervention Type DRUG

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

MARIAL® alone

Intervention Type DEVICE

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

Interventions

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MARIAL® + PPI (generic Omeprazole)

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

Intervention Type COMBINATION_PRODUCT

PPI alone (generic omeprazole)

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

Intervention Type DRUG

MARIAL® alone

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

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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).
* Presence of any clinically significant medical condition judged by the investigator to preclude the patient's inclusion in the study for its safety
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Opera CRO, a TIGERMED Group Company

OTHER

Sponsor Role collaborator

Nekkar Lab Srl

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Doina Rosu

Role: PRINCIPAL_INVESTIGATOR

Societatea Civilă Medicală Gados

Locations

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UOC Endoscopia Digestiva Chirurgica Policlinico Gemelli - Universita Cattolica

Roma, , Italy

Site Status RECRUITING

Cabinet Particular Policlinic Algomed

Timișoara, Timiș County, Romania

Site Status COMPLETED

Societatea Civilă Medicală Gados

Timișoara, , Romania

Site Status COMPLETED

Medlife SA

Timișoara, , Romania

Site Status COMPLETED

Centrul Medical Salvosan Ciobanca

Zalău, , Romania

Site Status COMPLETED

Countries

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Italy Romania

Central Contacts

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Barattini Dionisio Franco

Role: CONTACT

Phone: +39 3355437574

Email: [email protected]

Dogaru Dumitru-Emanuel

Role: CONTACT

Phone: +40 724345115

Email: [email protected]

Facility Contacts

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Guido Costamagna, MD, Prof

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 23853213 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29110162 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19703345 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28702984 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24117649 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29687692 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28859358 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26909885 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12150380 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17539985 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40649167 (View on PubMed)

Other Identifiers

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2019-004062-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NEK/MD/0119

Identifier Type: -

Identifier Source: org_study_id