Clinical trial NCT03793556: Evaluation of GERDOFF Efficacy in Combination With Proton Pump Inhibitor
Official title: Evaluation of the Effects of GERDOFF in Combination With a 6-week Therapy Based on Proton Pump Inhibitors Versus Proton Pump Inhibitors Alone on GERD-high Symptoms in Patients With Primary Diagnosis of Gastroesophageal Reflux Disease.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gastro-oesophageal Reflux Disease
Lead sponsor: SOFAR S.p.A.
Sponsor class: INDUSTRY
First posted: 2019-01-04
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients was randomized in an open-label treatment (in a ratio 1:1) and treated with the investigational medical device (IMD) + proton pump inhibitor (PPI) or PPI only for 6 weeks. At the end of treatment visit (V4) only patients who were classified as responders and belonging to the GERDOFF®+PPI group were included in the follow-up phase for 12 further weeks. During the follow-up, patients were randomized to an open-label treatment (in a 1:1 ratio) to GERDOFF® group or control group that will not receive any treatment for 12 weeks in order to evaluate the maintenance of treatment effects. To safeguard the health and well-being of patients, and to keep under control the possible upper symptoms of GERD that could appear, all patients that continued in the follow-up period received omeprazole as rescue medication, in a quantity adequate to cover the entire follow-up period.
Primary purpose: TREATMENT

Brief summary: The aim of the present study was to evaluate the effect of a 6-weeks treatment of a CE-marked combination oral formulation of hyaluronic acid with chondroitin sulphate and aluminium hydroxide (GERDOFF®), in addition to proton pump inhibitors (PPI) at the standard dose, versus PPI only, in patients with first diagnosed clinical presentation of extra-esophageal GERD symptoms.

The investigators verified the reduction of symptoms frequency, using a Likert questionnaire, and severity, using the Reflux Symptom Index (RSI) questionnaire, to evaluate the proportion of Responders and Non-Responder patients in these two groups after 6 weeks of treatment, compared to baseline. Moreover investigators evaluated the persistence of effects of GERDOFF® + PPI treatment on extraesophageal symptoms, after a 12-weeks follow up, only in responder patients.

Detailed description: Cough, hoarseness, prolonged voice lowering, and vocal timbre modification, without any documentable cause, are considered as minor disorders for which patients do not receive adequate attention. These disorders may represent extra-esophageal manifestations of gastro-oesophagea reflux. Accurate diagnosis and gastro-oesophageal reflux therapy have been proved as useful to improve patients' quality of life.

The aim of the present study was to evaluate, in first diagnosed patients presenting with upper symptoms associated with GERD, the effect of a 6-week treatment with a combination based on CS, HA and aluminium hydroxide (Gerdoff®), co-administered with a treatment with PPIs, compared to treatment with PPIs as monotherapy, i.e. to verify, in patients treated with the combination of the two products, the reduction in symptoms frequency by means of a Likert questionnaire and the severity of upper symptoms by means of the Reflux Symptom Index (RSI) questionnaire, and to collect safety data. After 6 weeks of treatment, patients included in the two groups were then classified as responders or non-responders. Responder patients were defined as those patients that, at the 6th week of treatment, reached a RSI score decreased for at least 50% compared to baseline and an absolute value \< 13.

Furthermore, the maintenance of the effect of treatment on the extra-oesophageal symptoms was evaluated after a period of follow-up lasting 12 weeks, which could be entered only by responder patients randomised in the Gerdoff®-PPI arm. Patients included in the follow-up period were randomised to receive Gerdoff® or no treatment (control group). Safety data were also evaluated in the group of patients that continued in the follow-up period.

Eligibility criteria: Inclusion Criteria:

1. Male or female subjects aged ≥ 18 years;
2. First diagnosis of GERD with upper symptoms, made on a clinical basis and confirmed by an ENT and/or confirmed by a Gastroenterologist using a RSI questionnaire;
3. Presence of extra-oesophageal symptoms associated with GERD;
4. RSI score ≥ 20;
5. Patients not pre-treated with PPIs, even for problems different from GERD, and/or with medical devices and/or similar products (e.g. antacid alginates etc..) in the last 4 weeks;
6. Cooperative patients, able to understand and adhere to the study procedures;
7. Patient able to freely give their written informed consent to study participation;
8. Patients that freely gave the consent to management of personal data related to the study.

Exclusion Criteria:

1. Known infective oesophagitis or oesophagitis due to acid or alkaline substances;
2. Acute or chronic rhinosinusitis;
3. Chronic bronchitis;
4. Known Zollinger-Ellison syndrome, hiatal hernia greater than 3 cm and Barrett oesophagus;
5. Ongoing neoplasias;
6. Uncontrolled diabetes;
7. Patients with impaired liver function;
8. Patients with rare hereditary problems of galactose intolerance;
9. Patients that, based on Investigator's opinion, could not take part in the study due to other diseases or concomitant therapies, such as the intake of atazanavir, nelfinavir, clopidogrel, posaconazole and erlotinib (as recommended in the Summary of Product Characteristics of Gerdoff®);
10. Patients with deficiency of Lapp lactase;
11. Patients with syndrome of glu-gal malabsorption;
12. Patients with hypersensitivity to omeprazole, substitute benzymidazolic or any of the excipients;
13. Patients already in treatment with PPIs or similar products;
14. Chronic use of drugs that interfere with the salivary secretion (e.g. anti-histamines or inhaled steroids);
15. Abuse of drug or alcohol;
16. Inability of the subject to adequately express his/her disturbances;
17. Patients with planned or ascertained pregnancy or that did not adopt an accepted contraceptive method;
18. Lactating patients.

Primary outcomes:
measure: Change From Baseline to Visit V4 of the Total Score of RSI Questionnaire
timeFrame: In the first visit (baseline) and in the visit 4 (after 6 weeks of treatment)
Secondary outcomes:
measure: Total Score of Reflux Symptom Index Questionnaire in All Time-points Assessed
timeFrame: In baseline Visit, Visit 2 (after 1 week), Visit 3 (after 3 weeks) and Visit 4 (after 6 weeks of treatment)
measure: Score of Hoarseness or Vocal Problem of the RSI Questionnaire Measured at the Baseline and in the Visit 4
timeFrame: At baseline and in the visit 4, after 6 weeks of treatment
measure: Score of Throat of the RSI Questionnarie Measured at the Baseline and in the Visit 4 of the RSI Questionnaire Score of Throat Clearance
timeFrame: At baseline and in the visit 4, after 6 weeks of treatment
measure: Score of Excess of Mucus in the Throat or Retrosternal Fall of Secretions of the RSI Questionnaire Measured at Baseline and in the Visit 4
timeFrame: At baseline and in the visit 4, after 6 weeks of treatment
measure: Score of Difficulty in Swallowing Food, Fluids or Pills of the RSI Questionnaire Measured at Baseline and in the Visit 4
timeFrame: At baseline and in the visit 4, after 6 weeks of treatment
measure: Score of Cough of the RSI Questionnaire Measured at Baseline and in the Visit 4 After the Meal or After Lying
timeFrame: At baseline and in the visit 4, after 6 weeks of treatment
measure: Score of Difficulty in Breathing or Episodes of Choking of the RSI Questionnaire Measured at Baseline and in the Visit 4
timeFrame: At baseline and in the visit 4, after 6 weeks of treatment
measure: Score of Problematic or Troublesome Cough of the RSI Questionnaire Measured at Baseline and in the Visit 4
timeFrame: At baseline and in the visit 4, after 6 weeks of treatment
measure: Score of Sensation of Something Blocked or Mass in the Throat of the RSI Questionnaire Measured at Baseline and in the Visit 4
timeFrame: At baseline and in the visit 4, after 6 weeks of treatment
measure: Score of Stomach Burning, Thoracic Pain, Poor Digestion of Gastric Acid That Moves Upright of the RSI Questionnaire Measured at Baseline and in the Visit 4
timeFrame: At baseline and in the visit 4, after 6 weeks of treatment
measure: Number of Responders V4
timeFrame: At visit 4 after 6 weeks of treatment
measure: Number of Responders V6
timeFrame: In the Visit 6 at the end of follow-up
measure: Score of Upper Symptoms Using the Likert Scale at Baseline and in the Visit V4
timeFrame: At baseline and in the visit 4
measure: Presence of Upper Symptoms at Visit 4, Using the RSI Questionnaire
timeFrame: At visit 4 after weeks of treatment
measure: Use of Rescue Medication (Omeprazole) During the Treatment
timeFrame: From baseline to visit 4
measure: Use of Rescue Medication (Omeprazole) During the Follow-up
timeFrame: In the Visit 6 after 12 weeks from baseline
measure: Use of Rescue Medication (Other Than Omeprazole) During Treatment
timeFrame: From baseline to visit 4
measure: Patients'Satisfaction
timeFrame: At visit 4 after weeks of treatment
Other outcomes:
Locations:
city: Rozzano
country: Italy
facility: dr Alessandro Repici
state: MI
Study officials:
affiliation: Istituto Clinico Humanitas
name: Alessandro Repici, MD
role: PRINCIPAL_INVESTIGATOR
References: