Clinical trial NCT04130659: Study to Evaluate the Performance and Safety of the MARIAL® in Association With PPI Versus PPI Alone
Official title: Open, Comparative Study To Evaluate The Performance And Safety Of The Medical Device Marial® In Association With Proton-Pump Inhibitors Versus PPI Alone In Patients Affected By Gastroesophageal Reflux Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Gastroesophageal Reflux Disease (GERD)
Keywords: Medical Device
Proton-pump inhibitor
Gastroesophageal Reflux Disease
Magnesium Alginate
Mucosal protective agent
Lead sponsor: Nekkar Lab Srl
Sponsor class: INDUSTRY
Collaborators: name: Opera CRO, a TIGERMED Group Company
First posted: 2019-10-17
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: TREATMENT

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®.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Total Gaviscon® tablets consumption by patients using alginate as rescue medication
timeFrame: 28 days
Secondary outcomes:
measure: Reflux Symptoms Index (RSI)
timeFrame: 180 days
measure: GERD Impact Scale (GIS)
timeFrame: 180 days
measure: GERD Health-Related Quality of Life (GERD-HRQL)
timeFrame: 180 days
measure: Investigator Global Assessment of the Performance (IGAP)
timeFrame: 180 days
measure: Investigator Global Assessment of Safety (IGAS)
timeFrame: 180 days
measure: Serious Adverse Device Effects (SADE), Serious Adverse Events (SAE), Adverse Device Effects (ADE), Adverse Events (AE), and Device Deficiency (DD)
timeFrame: 180 days
measure: Esophagogastroduodenoscopy (EGD)
timeFrame: 28 days
measure: GERD recurrence rate
timeFrame: 150 days
Other outcomes:
Locations:
city: Roma
country: Italy
facility: UOC Endoscopia Digestiva Chirurgica Policlinico Gemelli - Universita Cattolica
city: Timișoara
country: Romania
facility: Cabinet Particular Policlinic Algomed
state: Timis
city: Timişoara
country: Romania
facility: Societatea Civilă Medicală Gados
city: Timişoara
country: Romania
facility: Medlife SA
city: Zalău
country: Romania
facility: Centrul Medical Salvosan Ciobanca
Study officials:
affiliation: Societatea Civilă Medicală Gados
name: Doina Rosu
role: PRINCIPAL_INVESTIGATOR
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citation: 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.
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