Research for Prevention and Treatment of NSAIDs Related Gastrointestinal Side Effects

NCT ID: NCT01547559

Last Updated: 2014-10-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 369 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-30

Brief Summary

We aim to evaluate the protective effects of eradication of HP and continue using Geranylgeranylacetone (GGA) on NSAIDs related gastroenterological lesions. We further aim to explore the effect of GGA on small-intestinal mucosal injuries induced by diclofenac sodium in patients with rheumatic diseases who didn't take NSAIDs in the preceding 6 months.

Detailed Description

NSAIDs are mainly used drugs in rheumatic disease and cardiologic disease. However the gastroenterological lesions prevent patients get benefits from continuing taking NSAIDs. HP is another important factor that increase gastroenterological lesions. Both HP and NSAIDs increase risk of peptic ulcers, however, no exact relation between these two factors has been found. It is important to evaluate the protective effects of eradication of HP in NSAIDs-taking patients. In many countries ,PPI is recommended as maintain treatment in NSAIDs-taking patients to prevent gastroenterological lesions. A multicenter, open-label, randomized, parallel-group study is needed to prove the effects of Teprenone as a replacer of PPI in maintain treatment.On the other hand, Small-intestinal mucosal injuries induced by non-steroidal anti-inflammatory drugs (NSAIDs) are common. However, there are still no effective and reliable interventions established. Geranylgeranylacetone (GGA) is a mucosal protective agent, so we develop an additional trail to clarify the discrepancies of GGA effects on NSAIDs-induced small-intestinal mucosal injuries.

Conditions

Non-steroidal Anti-inflammatory Drug Adverse Reaction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

part1:blank control

NO maintain drugs with Hp negative patients.

Group Type: NO_INTERVENTION

No interventions assigned to this group

part1:teprenone 1

maintain treatment with Teprenone for Hp negative patients

Group Type: EXPERIMENTAL

part1:teprenone

Intervention Type: DRUG

Teprenone 50mg tid after meal for Hp negative patients.

part1:EAC-T

eradication of Hp with triple treatment

Group Type: EXPERIMENTAL

part1:EAC-T

Intervention Type: DRUG

esomeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg, each twice daily followed by gastric mucosal protective therapy with teprenone 50mg three times daily for 11 weeks

part1：EA-EMC-T

eradication of Hp with sequential therapy

Group Type: EXPERIMENTAL

part1:EA-EMC-T

Intervention Type: DRUG

esomeprazole 20 mg plus amoxicillin 1 g, twice daily for 5 days, then esomeprazole 20 mg with clarithromycin 500 mg and metronidazole 500 mg, twice daily for another 5 consecutive days) followed by teprenone 50mg three times daily until 12 weeks

part1：T-T

Teprenone as maintain drugs for Hp positive patients

Group Type: ACTIVE_COMPARATOR

part1:teprenone

Intervention Type: DRUG

Teprenone 50mg tid after meal for Hp positive patients.

part2:GGA group

Geranylgeranylacetone plus diclofenac sodium for patients with rheumatic diseases

Group Type: EXPERIMENTAL

part2:GGA group

Intervention Type: DRUG

GGA 50mg three times daily plus diclofenac sodium 75mg once a day for patients with rheumatic diseases.

part2:control group

diclofenac sodium only for patients with rheumatic diseases

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

part1:teprenone

Teprenone 50mg tid after meal for Hp negative patients.

Intervention Type: DRUG

part1:EAC-T

esomeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg, each twice daily followed by gastric mucosal protective therapy with teprenone 50mg three times daily for 11 weeks

Intervention Type: DRUG

part1:EA-EMC-T

esomeprazole 20 mg plus amoxicillin 1 g, twice daily for 5 days, then esomeprazole 20 mg with clarithromycin 500 mg and metronidazole 500 mg, twice daily for another 5 consecutive days) followed by teprenone 50mg three times daily until 12 weeks

Intervention Type: DRUG

part1:teprenone

Teprenone 50mg tid after meal for Hp positive patients.

Intervention Type: DRUG

part2:GGA group

GGA 50mg three times daily plus diclofenac sodium 75mg once a day for patients with rheumatic diseases.

Intervention Type: DRUG

Other Intervention Names

teprenone treatment; EAC-T treatment; EA-EMC-T treatment; T-T treatment; GGA

Eligibility Criteria

Inclusion Criteria

1. informed consents be given before treatment

2. NSAIDs taking patients

3. not taking PPI or other digestive drugs during previous 1 months

4. age ranging from 18～80 years old

1.18 to 65 years of age 2.patients with rheumatic diseases such as ankylosing spondylitis , rheumatoid arthritis and undifferentiated arthritis 3.planning to take diclofenac sodium for at least 12 weeks 4.having freely been given their fully informed consent based on their full understanding

Exclusion Criteria

1. having any severe acute or chronic complications

2. renal dysfunction, blood creatinine≥150µmol/L

3. blood aminotransferase level rising up(more than 2 times of the normal level)

4. any severe cardiac disease including congestive cardiac failure, unstable angina and myocardial infarct in 12 months

5. serious hypertension (systolic pressure≥180mmHg and/ or diastolic pressure≥110mmHg)

6. chronic or acute pancreatic disease

7. severe systematic diseases or malignant tumor

8. allergic to the drugs using in the trial

9. any factors interfering the result

10. female patients incline to be pregnant

11. being treated with drugs influencing gastroenterological conditions.

12. poor compliance part2:

1. Patients were excluded if they had a history of peptic ulcer or gastrointestinal bleeding

2. had serious liver, kidney, heart, or lung disease

3. had suspected small-bowel obstruction

4. had a history of gastrointestinal surgery except for appendectomy

5. had a drug addiction or alcoholism; were pregnant or hoped to become pregnant during the study period

6. were taking anti-secretory drugs such as PPIs or H2 receptor antagonists (H2RA), or other gastric mucosal protective drugs

7. had a lack of consent to the surgery required if the capsule endoscope was retained in the body

8. were judged to be inappropriate for this study by the investigator

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Xinxin Huang

doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Minhu Chen, MD PHD

Role: STUDY_CHAIR

First Affiliated Hospital, Sun Yat-Sen University

Locations

the first Affiliated Hospital of Sun Yat-Sen university

Guangzhou, Guangdong, China

the first Affiliated Hospital of Sun Yat-Sen university

Guangzhou, Guangdong, China

Countries

China

References

Xiong L, Huang X, Li L, Yang X, Liang L, Zhan Z, Ye Y, Chen M. Geranylgeranylacetone protects against small-intestinal injuries induced by diclofenac in patients with rheumatic diseases: a prospective randomized study. Dig Liver Dis. 2015 Apr;47(4):280-4. doi: 10.1016/j.dld.2015.01.005. Epub 2015 Jan 20.

Reference Type: DERIVED

PMID: 25660821 (View on PubMed)

Other Identifiers

5010-2007005

Identifier Type: -

Identifier Source: org_study_id