Clinical trial NCT02670642: Open, Randomised, Multi-center Study of on Demand Versus Continuous Esomeprazole Treatment in Patient With GERD
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastroesophageal Reflux
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2016-02-02
Enrollment: 877
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 6 months
Secondary outcomes:
measure: Reasons for discontinuation of on-demand or continuous esomeprazole treatment assessed by investigator-completed questionnaire at clinical visits
timeFrame: 6 months
measure: Mean number of esomeprazole tablets taken measured using the Medical Event Monitoring System (MEMS) container (date and time of use recorded)
timeFrame: 6 months
measure: 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
timeFrame: 6 months
measure: 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
timeFrame: 6 months
measure: 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)
timeFrame: 6 months
measure: Individual patterns of esomeprazole tablet usage measured using the Medical Event Monitoring System (MEMS) container (date and time of use recorded)
timeFrame: 6 months
measure: 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
timeFrame: 6 months
Other outcomes:
Locations:
city: Feldbach
country: Austria
facility: A.ö.Landeskrankenhaus Feldbach
city: Kittsee
country: Austria
facility: A.ö. Landeskrankenhaus Kittsee
city: Knittelfeld
country: Austria
facility: Spitalverbund Landeskrankenhaus
city: Wien
country: Austria
facility: Krankenhaus der Stadt Wien
city: Wien
country: Austria
facility: Hanusch Hospital
city: Zell am See
country: Austria
facility: A.ö. Krankenhaus Zell am See
city: Ales
country: France
facility: 36 boulevard Gambetta
city: Arras
country: France
facility: 84 rue Gustave Colin
city: Belfort
country: France
facility: 15 rue Michelet
city: Beziers
country: France
facility: 30 boulevard du Président John Kennedy
city: Cagnes Sur Mer
country: France
facility: 10 avenue Villeneuve
city: Cannes La Bocca
country: France
facility: 13 rue Roquebillière
city: Charenton Le Pont
country: France
facility: 91 rue de Paris
city: Clermont Ferrand
country: France
facility: 62 rue Bonnabaud
city: Creteil
country: France
facility: 17 villa du Petit Parc
city: Douai
country: France
facility: 24 quai Saint Maurand
city: Dreux
country: France
facility: 3 place du Marché Couvert
city: Epernay
country: France
facility: Clinique Saint Vincent
city: Epinal
country: France
facility: 7 rue Parmentier
city: Issoire
country: France
facility: Place du Postillon
city: Lille
country: France
facility: 60 rue Jean Bart
city: Montelimar
country: France
facility: 81 avenue du Teil
city: Nancy
country: France
facility: 9 square de Liège
city: Narbonne
country: France
facility: 6 avenue du Maréchal Juin
city: Paris
country: France
facility: 74 avenue Paul Doumer
city: Rouen
country: France
facility: 45bis rue d.Elbeuf
city: Saint Denis
country: France
facility: 64 boulevard Marcel Sembat
city: Saint Priest
country: France
facility: 31 rue Henri Maréchal
city: Talence
country: France
facility: 201 boulevard Robespierre
city: Velizy Villacoublay
country: France
facility: 4 rue Berlioz
city: Vitry Sur Seine
country: France
facility: 20 rue de la Glacière
city: Vitry Sur Seine
country: France
facility: 68 avenue Paul Vaillant Couturier
city: Berlin
country: Germany
facility: Wartburgstraße 19
city: Dresden
country: Germany
facility: Carl Gustav Carus der Tecnischen Universität
city: Freising
country: Germany
facility: Finkenstraße 31
city: Görlitz
country: Germany
facility: Reichenbacher Str. 106 a
city: Kronach
country: Germany
facility: Frankenwaldklinik
city: Köln
country: Germany
facility: Gemeinschaftspraxis
city: Köln
country: Germany
facility: Genovevastraße 5
city: Lienen
country: Germany
facility: Buchentorstr. 16
city: Münster
country: Germany
facility: Hammer Str. 108
city: Münster
country: Germany
facility: Albersloher Weg 455
city: Oelde
country: Germany
facility: Am Bahnhof 3
city: Potsdam
country: Germany
facility: Rudolf-Breitscheid-Str. 56
city: Ribnitz
country: Germany
facility: Musikantenweg 3
city: Wolmirstedt
country: Germany
facility: Friedensstr. 14
city: Bloemfontein
country: South Africa
facility: Gastroenterology Clinic, G73, Department of Internal Medicine, Universitas Hospital
city: Cape Town
country: South Africa
facility: Burnside House, Room 1
city: Cape Town
country: South Africa
facility: Gastroenterology Clinic, E23, Groote Schuur Hospital Observatory
city: Cape Town
country: South Africa
facility: Gastroenterology Clinic, Parorama Medi-Clinic
city: Cape Town
country: South Africa
facility: Gastroenterology Unit, Room C78, Tygerberg Hospital
city: Centurion
country: South Africa
facility: Unitas Hospital Lyttleton
city: Durban
country: South Africa
facility: Gastroenterology Clinic, Parklands Medical Centre
city: Johannesburg
country: South Africa
facility: Gastroenterology Clinic, Milpark Hospital
city: Johannesburg
country: South Africa
facility: Gastroenterology Unit, Chris Hani Baragwanath Hospital
city: Barcelona
country: Spain
facility: Centro Médico Teknon
city: Guadalajara
country: Spain
facility: Hospital General de Guadalajara
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena
Study officials:
affiliation: University Hospital Carl-Gustav-Carus, Medical Clinic and Policlinic I, Fetscherstr. 74, 01307 Dresden, Germany
name: Ekkehard Bayerdörffer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.