Efficacy and Safety Study of Esomeprazole 20mg qd vs Ranitidine 150mg Bid in Patients With an NSAID-induced Gastric Ulcer

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00401752
• Collaborator: (none)
• Enrollment: 397
• Locations: 9
• Duration (Months): 32.1
• Patients Per Site: 44.1
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy of esomeprazole 20 mg dosed once daily and ranitidine 150 mg dosed twice daily through 4 weeks of treatment for the healing of gastric ulcers in patients receiving daily non-steroidal anti-inflammatory drug (NSAID)therapy.

Condition or Disease	Intervention/Treatment	Phase
Gastric Ulcer	Drug: Esomeprazole; Drug: Ranitidine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 397 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Double-dummy, Parallel-group, 8 Week Comparative Efficacy and Safety Study of Esomeprazole 20 mg Every Day (qd) Versus Ranitidine 150 mg Twice a Day (Bid) in Patients With an NSAID-associated Gastric Ulcer When Daily NSAID is Continued
• Study Start Date: Mar 1, 2006
• Actual Study Completion Date: Nov 1, 2008

Outcome Measures

Primary Outcome Measures

1. The Percentage of Subjects Whose Gastric Ulcer(s) (GUs) Was (Were) Healed at Week 4 After Treatment With Esomeprazole 20 mg qd and Ranitidine 150 mg Bid in Patients Receiving Daily Non-steroidal Anti-inflammatory Drug (NSAID)Therapy. [4 weeks]

   Healed was defined as the absence of gastric ulcers. It was calculated as the proportion of subjects whose gastric ulcer(s) healed after 4 weeks treatment. (Ulcers were on S stage, stage 1 = Nonblanchable erythema of intact skin, stage 2 = Partial thickness skin loss involving epidermis, dermis, or both, stage 3 = Full thickness skin loss involving damage to or necrosis of subcutaneous tissue, stage 4 = Full thickness skin loss with extensive destruction, tissue necrosis, or damage to muscle, bone, or supporting structures or absent).

Secondary Outcome Measures

1. The Percentage of Subjects Whose Gastric Ulcer(s) Was (Were) Healed at Week 8 After Treatment With Esomeprazole 20 mg qd and Ranitidine 150 mg Bid in Patients Receiving Daily NSAID Therapy. [8 weeks]

   Healed was defined as the absence of gastric ulcers (Ulcers were on S stage or absent). It was calculated as the proportion of subjects whose gastric ulcer(s) healed after 8 weeks treatment.

2. The Resolution of Heartburn Symptoms at Week 4 and Week 8 After Treatment With Esomeprazole 20 mg qd and Ranitidine 150 mg Bid in Patients Receiving Daily NSAID Therapy. [week 4 and week 8]

   Resolution rate of investigator-assessed GI symptoms, including heartburn, acid regurgitation, nausea, abdominal fullness and sleep disorder. It was calculated as the percentage of subjects whose heartburn symptoms were resolved at Week 8.

3. Percentage of Participants With the Occurance of Any Adverse Event. [8 weeks]

   Safety evaluation including vital signs, physical examination, ECG, adverse events and clinical laboratory evaluations during 8 weeks treatment.

4. The Percentage of Participants Whose Duodenal Ulcer(s) (DUs) Was (Were) Healed at Week 4 and Week 8 After Treatment With Esomeprazole 20 mg qd and Ranitidine 150 mg Bid in Patients Receiving Daily NSAID Therapy. [4 and 8 week]

   Healed was defined as the absence of ulcers (Ulcers were on S stage or absent). It was calculated as the proportion of subjects whose duodenal ulcer healed after 4 and 8 weeks treatment.

5. The Percentage of Participants Whose GU(s) and DU(s) in Combination Were Healed at Week 4 and Week 8 After Treatment With Esomeprazole 20 mg qd and Ranitidine 150 mg Bid in Patients Receiving Daily NSAID Therapy [4 & 8 weeks]

   Healed was defined as the absence of ulcers (Ulcers were on S stage or absent). It was calculated as the proportion of subjects whose gastric and duodenal ulcer healed after 4 and 8 weeks treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed informed consent.

• A clinical diagnosis of a chronic condition that requires daily NSAID treatment for at least 2 months.

• Daily NSAID dose and type must have been stable for at least 2 weeks prior to the baseline endoscopy;orally;

Exclusion Criteria:

• History of esophageal, gastric or duodenal surgery, except for simple closure of an ulcer.

• History of severe liver disease, including (but not limited to) cirrhosis and acute or chronic hepatitis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Fuzhou	Fujian	China
2	Research Site	Guangzhou	Guangdong	China
3	Research Site	Wuhan	Hubei	China
4	Research Site	Suzhou	Jiangsu	China
5	Research Site	Shenyang	Liaoning	China
6	Research Site	Xi'an	Shanxi	China
7	Research Site	Beijing		China
8	Research Site	Shanghai		China
9	Research Site	Hong Kong		Hong Kong

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: Tore Lind, MD, AstraZeneca

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00401752
• Other Study ID Numbers: D9617L00001
• First Posted: Nov 22, 2006
• Last Update Posted: Jul 8, 2010
• Last Verified: Jun 1, 2010

• Keywords provided by , ,: NSAID-associated gastric ulcer
• Additional relevant MeSH terms: Stomach Ulcer; Ulcer; Esomeprazole; Ranitidine; Ranitidine bismuth citrate

Study Results

Participant Flow

Recruitment Details	Total 219 patients from 18 centers in China who had been receiving a stable daily dose of 1 or more NSAIDs for at least 2 weeks and who had an NSAID-associated GU verified by EGD at baseline were randomized. The first patient was enrolled on 31 Mar 2006, the last patient was completed on 17 Nov 2008.
Pre-assignment Detail	Total 397 patients from 24 centers in China were enrolled. 178 patients were not randomised due to unwillingness to continue the study or development of any exclusion criteria, etc. Total 219 patients were randomised, 217 patients were included in ITT population.

Arm/Group Title	Esomeprazole	Ranitidine
Arm/Group Description	Esomeprazole 20 mg tablet qd oral administration	ranitidine 150 mg capsule bid oral administration
Period Title: Overall Study
STARTED	107	112
Number of Patients Received Treatment	107	111
Patients Included in ITT Population	106	111
Patients Included in Safety Population	107	110
Patients Included in Per-Protocol Popula	100	99
COMPLETED	97	94
NOT COMPLETED	10	18

Baseline Characteristics

Arm/Group Title	Esomeprazole	Ranitidine	Total
Arm/Group Description	Esomeprazole 20 mg tablet qd oral administration	ranitidine 150 mg capsule bid oral administration	Total of all reporting groups
Overall Participants	106	111	217
Age (year) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [year]	49.7 (11.01)	50.9 (10.2)	50.3 (10.6)
Sex: Female, Male (Count of Participants)
Female	51 48.1%	53 47.7%	104 47.9%
Male	55 51.9%	58 52.3%	113 52.1%

Outcome Measures

1. Primary Outcome

Title	The Percentage of Subjects Whose Gastric Ulcer(s) (GUs) Was (Were) Healed at Week 4 After Treatment With Esomeprazole 20 mg qd and Ranitidine 150 mg Bid in Patients Receiving Daily Non-steroidal Anti-inflammatory Drug (NSAID)Therapy.
Description	Healed was defined as the absence of gastric ulcers. It was calculated as the proportion of subjects whose gastric ulcer(s) healed after 4 weeks treatment. (Ulcers were on S stage, stage 1 = Nonblanchable erythema of intact skin, stage 2 = Partial thickness skin loss involving epidermis, dermis, or both, stage 3 = Full thickness skin loss involving damage to or necrosis of subcutaneous tissue, stage 4 = Full thickness skin loss with extensive destruction, tissue necrosis, or damage to muscle, bone, or supporting structures or absent).
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole	Ranitidine
Arm/Group Description	Esomeprazole 20 mg tablet qd oral administration	ranitidine 150 mg capsule bid oral administration
Measure Participants	106	111
Number [Percentage of participants]	59.4 56%	59.5 53.6%

2. Secondary Outcome

Title	The Percentage of Subjects Whose Gastric Ulcer(s) Was (Were) Healed at Week 8 After Treatment With Esomeprazole 20 mg qd and Ranitidine 150 mg Bid in Patients Receiving Daily NSAID Therapy.
Description	Healed was defined as the absence of gastric ulcers (Ulcers were on S stage or absent). It was calculated as the proportion of subjects whose gastric ulcer(s) healed after 8 weeks treatment.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole	Ranitidine
Arm/Group Description	Esomeprazole 20 mg tablet qd oral administration	ranitidine 150 mg capsule bid oral administration
Measure Participants	106	111
Number [Percentage of participants]	81.1 76.5%	73.9 66.6%

3. Secondary Outcome

Title	The Resolution of Heartburn Symptoms at Week 4 and Week 8 After Treatment With Esomeprazole 20 mg qd and Ranitidine 150 mg Bid in Patients Receiving Daily NSAID Therapy.
Description	Resolution rate of investigator-assessed GI symptoms, including heartburn, acid regurgitation, nausea, abdominal fullness and sleep disorder. It was calculated as the percentage of subjects whose heartburn symptoms were resolved at Week 8.
Time Frame	week 4 and week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole	Ranitidine
Arm/Group Description	Esomeprazole 20 mg tablet qd oral administration	ranitidine 150 mg capsule bid oral administration
Measure Participants	106	111
Number [Percentage of participants]	100 94.3%	97.7 88%

4. Secondary Outcome

Title	Percentage of Participants With the Occurance of Any Adverse Event.
Description	Safety evaluation including vital signs, physical examination, ECG, adverse events and clinical laboratory evaluations during 8 weeks treatment.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Patients included in safety population

Arm/Group Title	Esomeprazole	Ranitidine
Arm/Group Description	Esomeprazole 20 mg tablet qd oral administration	ranitidine 150 mg capsule bid oral administration
Measure Participants	107	110
Number [Percentage of participants]	16.8 15.8%	22.7 20.5%

5. Secondary Outcome

Title	The Percentage of Participants Whose Duodenal Ulcer(s) (DUs) Was (Were) Healed at Week 4 and Week 8 After Treatment With Esomeprazole 20 mg qd and Ranitidine 150 mg Bid in Patients Receiving Daily NSAID Therapy.
Description	Healed was defined as the absence of ulcers (Ulcers were on S stage or absent). It was calculated as the proportion of subjects whose duodenal ulcer healed after 4 and 8 weeks treatment.
Time Frame	4 and 8 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole	Ranitidine
Arm/Group Description	Esomeprazole 20 mg tablet qd oral administration	ranitidine 150 mg capsule bid oral administration
Measure Participants	15	22
Number [Percentage of participants]	93.3 88%	81.8 73.7%

6. Secondary Outcome

Title	The Percentage of Participants Whose GU(s) and DU(s) in Combination Were Healed at Week 4 and Week 8 After Treatment With Esomeprazole 20 mg qd and Ranitidine 150 mg Bid in Patients Receiving Daily NSAID Therapy
Description	Healed was defined as the absence of ulcers (Ulcers were on S stage or absent). It was calculated as the proportion of subjects whose gastric and duodenal ulcer healed after 4 and 8 weeks treatment.
Time Frame	4 & 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole	Ranitidine
Arm/Group Description	Esomeprazole 20 mg tablet qd oral administration	ranitidine 150 mg capsule bid oral administration
Measure Participants	106	111
Number [Percentage of participants]	80.2 75.7%	69.4 62.5%

Adverse Events

Arm/Group Title	Esomeprazole		Ranitidine
Arm/Group Description	Esomeprazole 20 mg tablet qd oral administration		ranitidine 150 mg capsule bid oral administration
All Cause Mortality
	Esomeprazole		Ranitidine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Esomeprazole		Ranitidine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/107 (1.9%)		2/110 (1.8%)
Gastrointestinal disorders
Gastric Cancer	2/107 (1.9%)		0/110 (0%)
GU Haemorrhage	0/107 (0%)		1/110 (0.9%)
Skin and subcutaneous tissue disorders
Erythrodermic Psoriasis	0/107 (0%)		1/110 (0.9%)
Other (Not Including Serious) Adverse Events
	Esomeprazole		Ranitidine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/ (NaN)		16/ (NaN)
Gastrointestinal disorders
Gastritis erosive	3/107 (2.8%)		4/110 (3.6%)
Gastric ulcer	2/107 (1.9%)		1/110 (0.9%)
Abdominal pain upper	1/107 (0.9%)		2/110 (1.8%)
Duodenal ulcer	0/107 (0%)		2/110 (1.8%)
Hepatobiliary disorders
Alanine aminotransferase increased	2/107 (1.9%)		0/110 (0%)
Aspartate aminotransferase increased	2/107 (1.9%)		0/110 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric Cancer	2/107 (1.9%)		0/110 (0%)
Nervous system disorders
Dizziness	0/107 (0%)		5/110 (4.5%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection	1/107 (0.9%)		2/110 (1.8%)

Limitations/Caveats

According to the protocol, the sample size was 320 patients which could achieve 80% power of superiority. Since the patient recruitment is very difficult, total 219 patients were randomized in present study, the power decreased to 60%

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.