Open, Randomised, Multi-center Study of on Demand Versus Continuous Esomeprazole Treatment in Patient With GERD (NEED)

On Demand vs Continuous Treatment of Endoscopy Negative Subjects With Gastroesophageal Reflux Disease (GERD) With Esomeprazole 20-mg Once Daily Over a 6 Months Long Term Treatment Phase. An Open, Randomised, Multicenter Study. NEED.

The purpose of this study is to compare on demand with continuous treatment of endoscopy negative subjects with gastroesophageal reflux disease (GERD), with esomeprazole 20-mg once daily, with regards to willingness to continue in the study as a result of satisfactory treatment over a six-month long term management period, after initial symptom relief.

Study Overview

• Status: Completed
• Conditions: Gastroesophageal Reflux
• Intervention / Treatment: Drug: Esomeprazole

• Study Type: Interventional
• Enrollment (Actual): 877
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Feldbach, Austria, A-8330
    • A.ö.Landeskrankenhaus Feldbach
  • Kittsee, Austria, A-2421
    • A.ö. Landeskrankenhaus Kittsee
  • Knittelfeld, Austria, A-8720
    • Spitalverbund Landeskrankenhaus
  • Wien, Austria, A-1030
    • Krankenhaus der Stadt Wien
  • Wien, Austria, A-1140
    • Hanusch Hospital
  • Zell am See, Austria, A-5700
    • A.ö. Krankenhaus Zell am See
• France
  • Ales, France, 30100
    • 36 boulevard Gambetta
  • Arras, France, 62000
    • 84 rue Gustave Colin
  • Belfort, France, 90000
    • 15 rue Michelet
  • Beziers, France, 34500
    • 30 boulevard du Président John Kennedy
  • Cagnes Sur Mer, France, 06800
    • 10 avenue Villeneuve
  • Cannes La Bocca, France, 06150
    • 13 rue Roquebillière
  • Charenton Le Pont, France, 94220
    • 91 rue de Paris
  • Clermont Ferrand, France, 63000
    • 62 rue Bonnabaud
  • Creteil, France, 94000
    • 17 villa du Petit Parc
  • Douai, France, 59500
    • 24 quai Saint Maurand
  • Dreux, France, 28100
    • 3 place du Marché Couvert
  • Epernay, France, 51205
    • Clinique Saint vincent
  • Epinal, France, 88000
    • 7 rue Parmentier
  • Issoire, France, 63500
    • Place du Postillon
  • Lille, France, 59000
    • 60 rue Jean Bart
  • Montelimar, France, 26200
    • 81 avenue du Teil
  • Nancy, France, 54500
    • 9 square de Liège
  • Narbonne, France, 11100
    • 6 avenue du Maréchal Juin
  • Paris, France, 75016
    • 74 avenue Paul Doumer
  • Rouen, France, 76000
    • 45bis rue d.Elbeuf
  • Saint Denis, France, 93200
    • 64 boulevard Marcel Sembat
  • Saint Priest, France, 69800
    • 31 rue Henri Maréchal
  • Talence, France, 33401
    • 201 boulevard Robespierre
  • Velizy Villacoublay, France, 78140
    • 4 rue Berlioz
  • Vitry Sur Seine, France, 94400
    • 20 rue de la Glacière
  • Vitry Sur Seine, France, 94400
    • 68 avenue Paul Vaillant Couturier
• Germany
  • Berlin, Germany, 10825
    • Wartburgstraße 19
  • Dresden, Germany, D-010307
    • Carl Gustav Carus der Tecnischen Universität
  • Freising, Germany, 85356
    • Finkenstraße 31
  • Görlitz, Germany, 02827
    • Reichenbacher Str. 106 a
  • Kronach, Germany, 96317
    • Frankenwaldklinik
  • Köln, Germany, 51065
    • Gemeinschaftspraxis
  • Köln, Germany, 51065
    • Genovevastraße 5
  • Lienen, Germany, 49536
    • Buchentorstr. 16
  • Münster, Germany, 48153
    • Hammer Str. 108
  • Münster, Germany, 48167
    • Albersloher Weg 455
  • Oelde, Germany, 59302
    • Am Bahnhof 3
  • Potsdam, Germany, 14482
    • Rudolf-Breitscheid-Str. 56
  • Ribnitz, Germany, 18311
    • Musikantenweg 3
  • Wolmirstedt, Germany, 39326
    • Friedensstr. 14
• South Africa
  • Bloemfontein, South Africa
    • Gastroenterology Clinic, G73, Department of Internal Medicine, Universitas Hospital
  • Cape Town, South Africa
    • Burnside House, Room 1
  • Cape Town, South Africa
    • Gastroenterology Clinic, E23, Groote Schuur Hospital Observatory
  • Cape Town, South Africa
    • Gastroenterology Clinic, Parorama Medi-Clinic
  • Cape Town, South Africa
    • Gastroenterology Unit, Room C78, Tygerberg Hospital
  • Centurion, South Africa
    • Unitas Hospital Lyttleton
  • Durban, South Africa
    • Gastroenterology Clinic, Parklands Medical Centre
  • Johannesburg, South Africa
    • Gastroenterology Clinic, Milpark Hospital
  • Johannesburg, South Africa
    • Gastroenterology Unit, Chris Hani Baragwanath Hospital
• Spain
  • Barcelona, Spain, 08022
    • Centro Medico Teknon
  • Guadalajara, Spain, 19009
    • Hospital General de Guadalajara
  • Oviedo, Spain, 33006
    • Hospital Central de Asturias
  • Santiago de Compostela, Spain, 15706
    • Hospital Clínico Universitario
  • Sevilla, Spain, 41071
    • Hospital Virgen Macarena

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Symptoms suggestive of GERD, with heartburn as their predominant symptom (described as a burning feeling, rising from the stomach or lower part of the chest up towards the neck), for longer than 6 months.
• Heartburn occurring for 4 days or more during the last 7 days prior to endoscopy. Or, if PPI treatment has been started within the last 7 days prior to endoscopy, then heartburn occurring for 4 days or more during the last 7 days prior to start of PPI treatment
• Male or female, at least 18 years of age (for Austria, at least 19 years of age)
• Have given written informed consent
• Ability to read and write (literate)
• 7 symptom free (from heartburn) days in the last week prior to randomisation (day of visit not included)

Exclusion Criteria:

• Documented esophageal mucosal break
• History of esophageal, gastric or duodenal surgery, except closure and oversewing of an ulcer

• Chronic or recurrent abdominal pain associated with a chronic or recurrent bowel disturbance and/or bloating, that in the opinion of the investigator is likely to be due to irritable bowel syndrome or two or more of the following criteria:

  • Symptoms relieved by defecation
  • Symptoms associated with change in frequency of stools
  • Symptoms associated with change in form of stools
• Any significant "alarm symptoms" such as unintentional weight loss, haematemesis melaena, jaundice or any other sign indicating serious or malignant disease.

• Subjects with current or historical evidence of the following diseases/conditions

  • Zollinger Ellison syndrome
  • Primary esophageal motility disorder(s) i.e. achalasia, scleroderma, esophageal spasm
  • Complications of GERD such as esophageal stricture, ulcer and/or macroscopic Barrett's metaplasia (longer than 3 centimetres) or significant dysplastic changes in the esophagus
  • Evidence of upper gastrointestinal malignancy at the screening endoscopy
  • Gastric and/or duodenal ulcers within the last 2 years
  • Malabsorption
  • Malignancy, or significant cardiovascular, pulmonary, renal, pancreatic or liver disease as judged by the investigator
  • Unstable diabetes mellitus. Stable diabetes controlled on diet, oral agents or insulin is acceptable
  • Cerebrovascular disease, such as cerebral ischemia, infarction, haemorrhage or embolus
• Subjects using a PPI for more than 10 days in the last 28 days, prior to endoscopy
• Use of PPIs for more than 5 days in the last 7 days prior to endoscopy
• Subjects using daily H2-receptor antagonist, prokinetics recommended in the treatment of reflux symptoms or sucralfate during the 2 weeks prior to endoscopy and between the endoscopy and visit 1 and throughout the study

• Need for continuous concurrent therapy with

  • NSAIDs (including selective COX II antagonists, salicylates (unless<165 mg daily for cardiovascular prophylaxis)
  • anticholinergics
  • prostaglandin analogues
  • phenytoin
  • ketoconazole
  • itraconazole
  • warfarin and other vitamin K antagonists
• Pregnancy or lactation. Women of childbearing potential must maintain effective contraception during the study period as judged by the investigator (for Austria: Women of child-bearing potential may only be included when their pregnancy status is assessed by the investigator prior to entry and then at monthly basis. For South-Africa and Spain:

Women of child-bearing potential may only be included when their pregnancy status is assessed by the investigator prior to endoscopy)

• Use of any other investigational compound 28 days prior to start and during the study
• Requirement of an interpreter (illiterate)
• Alcohol and/or drug abuse or any condition associated with poor compliance, including expected non-co-operation, as judged by the investigator
• Previous participation in this study
• Contra-indications to study drugs, e.g. known or suspected allergy to esomeprazole and any other constituents of the formulation. Known hypersensitivity to substituted benzimidazole

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: On demand 20 mg esomeprazole; On demand treatment with 20-mg esomeprazole once daily when needed	Drug: Esomeprazole; Proton pump inhibitor; Other Names: Nexium
ACTIVE_COMPARATOR: Continuous 20 mg esomeprazole; Continuous treatment with 20 mg esomeprazole once daily	Drug: Esomeprazole; Proton pump inhibitor; Other Names: Nexium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference between the proportion of patients who discontinued on-demand esomeprazole treatment versus continuous esomeprazole treatment due to unsatisfactory treatment as determined by the investigator in consultation with the patient	Compare on demand (taken as needed by the patient to adequately control their reflux disease) with continuous treatment of endoscopy negative subjects with gastroesophageal reflux disease (GERD), with esomeprazole 20-mg once daily, with regards to willingness to continue in the study as a result of satisfactory treatment over a six-month long term management period, after initial symptom relief	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Reasons for discontinuation of on-demand or continuous esomeprazole treatment assessed by investigator-completed questionnaire at clinical visits	6 months
Mean number of esomeprazole tablets taken measured using the Medical Event Monitoring System (MEMS) container (date and time of use recorded)	6 months
Change from baseline in impact of reflux symptoms on health-related quality of life using pre-specified dimensions of the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire	6 months
Difference between the proportion of patients reporting treatment satisfaction with on-demand versus continuous esomeprazole treatment assessed by standard patient-completed electronic questionnaire at clinical visits and premature discontinuation	6 months
Frequency of adverse events and assessment of hematology (hemoglobin, leukocytes, thrombocytes) and clinical chemistry (creatinine, alkaline phosphate, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, total bilirubin)	6 months
Individual patterns of esomeprazole tablet usage measured using the Medical Event Monitoring System (MEMS) container (date and time of use recorded)	6 months
Change from baseline in impact of reflux symptoms on health-related quality of life using pre-specified dimensions of the Quality Of Life in Reflux And Dyspepsia (QOLRAD) questionnaire	6 months

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Ekkehard Bayerdörffer, MD, University Hospital Carl-Gustav-Carus, Medical Clinic and Policlinic I, Fetscherstr. 74, 01307 Dresden, Germany

Publications and helpful links

General Publications

• Bayerdorffer E, Bigard MA, Weiss W, Mearin F, Rodrigo L, Dominguez Munoz JE, Grundling H, Persson T, Svedberg LE, Keeling N, Eklund S. Randomized, multicenter study: on-demand versus continuous maintenance treatment with esomeprazole in patients with non-erosive gastroesophageal reflux disease. BMC Gastroenterol. 2016 Apr 14;16:48. doi: 10.1186/s12876-016-0448-x.

Study record dates

Study Major Dates

• Study Start: August 1, 2001
• Primary Completion (ACTUAL): November 1, 2002
• Study Completion (ACTUAL): November 1, 2002

Study Registration Dates

• First Submitted: December 11, 2015
• First Submitted That Met QC Criteria: January 28, 2016
• First Posted (ESTIMATE): February 2, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): February 2, 2016
• Last Update Submitted That Met QC Criteria: January 28, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Esomeprazole
• Other Study ID Numbers: D9612C00004