Study to Evaluate the Performance and Safety of the Marial in Association With PPI Versus PPI Alone
Study Details
Study Description
Brief Summary
The Research Question of the present study is the following: in a group of patients affected by GERD, 1-month treatment with PPI (omeprazole) and Marial® will significantly decrease the use of Gaviscon® as rescue medicine in comparison with patients treated with omeprazole alone.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
This is an open-label, comparative, multicenter study with two parallel group of subjects. The clinical investigation will be performed in six clinical sites.
The study population will include subjects affected by GERD with diagnosis of Grade A esophagitis on Los Angeles Classification System grades reflux esophagitis, confirmed by gastroscopy (done within 1 month prior baseline).
Marial® is a class IIa medical device (Directive 93/42/EEC), already marketed in several EU countries. This compound has been produced combining hyaluronic acid, hydrolyzed keratin mucoproteins, glycoproteins such as fibronectin, meso glycans and integrins, and viscous agents. It evidenced to actively regenerate the damaged tissue by repairing and regenerative properties on mucous membranes and by muco-adhesive and film-forming characteristics that allow to prolong the contact time with the mucous membranes and consequently to improve the effectiveness.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Marial® + PPI (generic omeprazole) Marial® + PPI (generic omeprazole) Application: following the Summary of Product Characteristics Marial®: 1 stick of Marial® twice a day after meals from day 1 to 28 Omeprazole 20 mg cps: once a day from day 1 to 28 |
Device: Marial® + PPI (generic omeprazole)
Marial®: 1 stick of Marial® twice a day after meals from day 1 to 28 Omeprazole 20 mg cps: once a day from day 1 to 28
|
| Active Comparator: PPI alone (generic omeprazole) PPI alone (generic omeprazole) Application following the Summary of Product Characteristics Omeprazole 20 mg cps: once a day from day 1 to 28 |
Other: PPI alone (generic omeprazole)
Omeprazole 20 mg cps: once a day from day 1 to 28
|
Outcome Measures
Primary Outcome Measures
- The number of rescue medicine used (Gaviscon®) [28 days]
The number of rescue medicine used (Gaviscon®) has been chosen as a primary efficacy outcome (or measured variable) to measure the performance. Adjunctive medications have been used extensively to evaluate PPI performance (9) and Gaviscon was already tested as add-on therapy in a randomized clinical trial (10). The primary outcomes will be analyzed as follows: • the number of used Gaviscon from baseline to final visit in each group separately and in the Marial® +PPI group in comparison with that occurred in PPI alone group;
Secondary Outcome Measures
- Reflux symptoms index [180 days]
Reflux symptoms index is a 9 question questionnaire where the biggest possible score is 45 and represents severe probleme and the lowest possible score is 0 and represent no problem. Reflux symptoms index (RSI) was considered positive if the score was >13
- Questionnaire for patient: GERD Impact Scale (GIS) [180 days]
It comprises nine questions regarding the frequency of the following over the previous week: acid-related symptoms, chest pain, extra-esophageal symptoms, the impact of symptoms on sleep, work, meals and social occasions, and the use of additional non-prescription medication. Four response options are provided to describe frequency over the previous two weeks: 1=none of the time, 2=a little of the time, 3=some of the time, and 4=all of the time.
- Investigator Global Assessment of the Performance (IGAP) scored by Investigator [180 days]
Investigator Global Assessment of the Performance (IGAP) scored by Investigator as: 1= very good performance, 2 = good performance, 3 = moderate performance and 4 = poor performance. IGAP will be evaluated at the last visit of 1st and 2nd period, only.
- GERD Health-Related Quality of Life (GERD-HRQL) [180 days]
GERD-HRQL scored as: 0 = No Symptoms, 1 = Noticeable, but not bothersome, 2 = Noticeable, bothersome, but not every day, 3 = Bothersome daily, 4 = Bothersome and affects daily activities, 5 = Incapacitating to do daily
- Investigator Global Assessment of Safety (IGAS) [180 days]
Investigator Global Assessment of Safety (IGAS): using the 4-point scale: 1= very good safety, 2 = good safety, 3 = moderate safety and 4 = poor safety. IGAS will be evaluated at the last visit of 1st and 2nd period, only.
- Patient Global Assessment of Safety (PGAS) [180 days]
Patient Global Assessment of Safety (PGAS): it will be reported by the subject in the patient diary using the 4-point scale: 1= very good safety, 2 = good safety, 3 = moderate safety and 4 = poor safety.
- Incidence of AE, ADE, SAE, SADE [180 days]
AE, ADE, SAE, SADE: they will be reported by the Investigators according to the current legislation. All adverse events will be collected by Investigators and evaluated considering the change from baseline.
- Evaluation by gastroscopy [180 days]
Evaluation by gastroscopy (only in a sample of 16 patients belonging to site 1). By this evaluation, it will be determined if the patients had a reduction of erosions in the esophageal mucosa
- Safety evaluation of all patients treated with Marial [180 days]
Evaluation of long term (6 months) safety in monotherapy with Marial®. All the AE, ADE, SAE, SADE will be reported by the Investigators according to the current legislation. All adverse events will be collected by Investigators and evaluated considering the change from baseline.
- GERD recurrence rate [180 days]
GERD recurrence rate after 6 months of monotherapy with Marial®
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or non-pregnant female, both aged ≥ 18 to ≤ 65 years.
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Diagnosis of GERD Grade A esophagitis on Los Angeles Classification System grades reflux esophagitis by:
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gastroscopy (done within 1-month prior baseline). (5);
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episodic heartburn and/or acid regurgitation (at least 3 times per week in the last 2 weeks);
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Body mass index of ≥ 18.5 to ≤ 36 kg/m2.
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Able to communicate adequately with the investigator and to comply with the requirements for the entire study.
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Capable of and freely willing to provide written informed consent prior to participating in the study.
Exclusion Criteria:
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Intake of PPI or Marial® during the last 28 days before the start of the study.
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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.
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Previously underwent acid-lowering surgery or other surgery of the oesophagus and/or upper gastrointestinal tract (excluding appendectomy, cholecystectomy and polypectomy).
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History of co-existing disease that affects the esophagus (e.g. Barrett's esophagus, Zollinger-Ellison syndrome, esophageal stricture).
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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.
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Documented presence of severe renal or hepatic insufficiency (i.e. GOT, GPT elevated over double the normal range).
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Known hypersensitivity to omeprazole, and/or Marial® and/or Gaviscon®.
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Concurrent (or within 30 days of study entry) participation in a clinical trial.
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Females who are pregnant, or planning a pregnancy, or lactating. Females of child bearing potential not using reliable methods of birth control.
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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).
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Receiving any of the following drugs within 2 weeks before the baseline: theophylline, bismuth salts, warfarin, phenytoin, tacrolimus, diazepam, cyclosporine, disulfiram, benzodiazepines, barbiturates, antineoplastic agents, erythromycin, clarithromycin, sucralfate, clopidogrel or protease inhibitors.
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Taking concomitant medications that rely on the presence of gastric acid for optimal bioavailability (e.g. ketoconazole, ampicillin esters or iron salts).
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Drug or alcohol abuse within 12 months of Day 0
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Malignancy (also leukemic infiltrates) within 5 years prior to Day 0 (except for treated basal cell/squamous cell carcinoma of the skin).
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Psychosis, schizophrenia, mania, depressive disorders, history of suicide attempt or suicidal ideation, or any other psychiatric illness (except for intermittent anxiety).
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Presence of any clinically significant medical condition judged by the investigator to preclude the patient's inclusion in the study for its safety
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UOC Endoscopia Digestiva Chirurgica Policlinico Gemelli - Universita Cattolica | Roma | Italy | 00168 | |
| 2 | Societatea Civilă Medicală Gados | Timişoara | Timis | Romania |
Sponsors and Collaborators
- Nekkar Lab Srl
- Opera CRO, a TIGERMED Group Company
Investigators
- Principal Investigator: Doina Rosu, Societatea Civilă Medicală Gados
Study Documents (Full-Text)
None provided.More Information
Publications
- Aragona SE, Mereghetti G, Bianchetti M, Mangiavillano B, Zurlo T, Lotti J, La Mantia I, França 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.
- Aragona SE, Mereghetti G, Ciprandi G. Gastric reflux: the therapeutical role of Marial® . J Biol Regul Homeost Agents. 2018 Jul-Aug;32(4):969-972.
- Belafsky PC, Postma GN, Koufman JA. Validity and reliability of the reflux symptom index (RSI). J Voice. 2002 Jun;16(2):274-7.
- Chandran S, Raman R, Kishor M, Nandeesh HP. The effectiveness of mindfulness meditation in relief of symptoms of depression and quality of life in patients with gastroesophageal reflux disease. Indian J Gastroenterol. 2019 Feb;38(1):29-38. doi: 10.1007/s12664-019-00940-z. Epub 2019 Mar 13.
- 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. Review.
- 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. Review.
- 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. Review.
- 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.
- 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. Review.
- Reimer C, Lødrup 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.
- 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.
- NEK/MD/0119