Clinical trial NCT01140828: A Study of Rabeprazole for Prevention of Non Steroidal Anti-inflammatory Drug -Associated Gastroduodenal Injury
Official title: A Double-blind Randomized Placebo Controlled Trial of Rabeprazole for Prevention of NSAID-associated Dyspepsia and Gastroduodenal Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoarthritis
Arthritis, Rheumatoid
Dyspepsia
Keywords: Arthritis
Bone pain
dyspepsia
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2010-06-10
Enrollment: 112
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 aim of this study is to determine whether rabeprazole is superior to placebo in preventing dyspepsia and gastroduodenal injury in subjects with osteoarthritis (OA) and/or rheumatoid arthritis (RA) and/or bone pain.

Detailed description: Non steroidal anti-inflammatory drugs (NSAIDs) are well known to increase the risk of gastroduodenal (GD) ulcer and its complications. Up to 40% of average-risk NSAID users suffer from dyspepsia without endoscopic evidence of gastroduodenal injury. It results a significant loss of productivity and impairment of Quality of Life (QoL). Proton pump inhibitors (PPIs) have been shown to be effective in preventing and reducing NSAID-induced GD injury. PPIs are believed to have a class effect but Rabeprazole, the least expensive PPI, is grossly under-utilized in this area .

Current Hospital Authority (HA) guidelines, however, only endorse the use of PPI in patients at high risk of ulcer bleeding. Since NSAID-induced dyspepsia is not an indication for PPI according to HA guidelines, those patients do not receive PPI for treatment.

Eligibility criteria: Inclusion Criteria:

* Outpatient or inpatient subjects with a clinical diagnosis of OA or RA or any bone pain
* Subjects expected to require regular anti-inflammatory therapy for arthritis symptom management
* Subjects should have no history of peptic ulcer complications
* Screening tests are negative for H pylori
* Subjects who test positive can be re-screened after eradication of H. pylori

Exclusion Criteria:

* History of gastrointestinal (GI) hemorrhage
* History of gastric or duodenal surgery
* Presence of erosive esophagitis, gastric-outlet obstruction
* Likelihood of requiring treatment during the study with drugs not permitted by the protocol
* Impaired hepatic function (SGPT (ALT) or serum glutamate oxaloacetate transaminase (SGOT) (AST) \> 2 x upper limit of normal) or renal function (serum creatinine \> 200 umol/l)
* Any other condition or baseline finding which, in the investigator's judgment, might increase risk to the subject or decrease the chance of obtaining satisfactory data to achieve study objectives
* Anemia with Hb \< 10 g/dL
* Suspected or clinical diagnosis of inflammatory bowel disease
* Congestive heart failure (NYHA class III- IV)
* Subjects considered to have a requirement for continued use of:

  * Corticosteroids (dose equivalent of prednisolone/ prednisone \>10mg daily stable dose)
  * disease-modifying antirheumatic drug (DMARDs) (unless stable dose for ≥ 12 weeks)
  * Iron replacement therapy (a dose \> 15mg elemental iron/day)
  * Iron replacement therapy (a dose \> 15mg elemental iron/day) or supplements for deficiency prevention (a dose ≤ 15mg elemental iron/day) due to anemia or any other reason
  * Double anti-platelet therapy (e.g. aspirin + Plavix)
  * Anti-coagulants
  * Anti-ulcer medications, e.g. sucralfate, H2 receptor antagonists (H2RAs), misoprostol, PPIs other than study medications
  * Sucralfate, misoprostol or regular H2 receptor antagonists (H2RAs) (\> 3 days/week)
  * COX-2 inhibitors
  * anti-ulcer medications or COX-2 selective inhibitor at screening allowed if treatments discontinued at this time

Primary outcomes:
measure: 12-week cumulative incidence of gastric/duodenal ulcer, >10 erosions or severe dyspepsia
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: Prince of Wales Hospital
state: Hong Kong
Study officials:
affiliation: Chinese University of Hong Kong
name: Francis K Chan, MD
role: PRINCIPAL_INVESTIGATOR
References: