Trial Outcomes & Findings for Stress Ulcer Prophylaxis of Intravenous Esomeprazole in Chinese Seriously Ill Patients (NCT NCT02157376)

Last Updated: 2017-03-10

Results Overview

Criteria for a clinically significant upper GI bleeding as: 1. Bright red blood per NG or OG tube that did not clear after NG or OG tube adjustment and 5 to 10 minutes of at least 100 ml lavage with room temperature normal saline-or, 2. Persistent gastroccult- positive coffee ground material During IMP treatment Day 1-2: Persistent gastroccult- positive coffee ground material for at least eight consecutive hours that did not clear with at least 100 ml of lavage with room temperature normal saline. During IMP treatment Day 3-14: Persistent gastroccult- positive coffee ground material in at least three consecutive gastric aspirates within 2 to 4 hours (at least 60 ±20 minutes apart), that did not clear with at least 100 ml of lavage with room temperature normal saline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

343 participants

Primary outcome timeframe

1-14 days

Results posted on

2017-03-10

Participant Flow

Overall, 343 patients were enrolled from 27 centres in China. The first patient entered the study on 15 July 2014 and the last patient completed the study on 18 February 2016. Of the 343 patients enrolled into the study, 311 (90.7%) patients were randomised to treatment.

32 patients were not randomised to treatment due to eligibility criteria not being fulfilled.

Participant milestones

Participant milestones
Measure	Esomeprazole iv Esomeprazole 40 mg bid 30 min intermittent infusion given for maximum 14 days	Cimetidine iv Cimetidine 300 mg 30 min bolus infusion, followed by iv Cimetidine continuous infusion (50 mg/h) given for maximum 14 days
Overall Study STARTED	155	156
Overall Study COMPLETED	133	138
Overall Study NOT COMPLETED	22	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Esomeprazole iv Esomeprazole 40 mg bid 30 min intermittent infusion given for maximum 14 days	Cimetidine iv Cimetidine 300 mg 30 min bolus infusion, followed by iv Cimetidine continuous infusion (50 mg/h) given for maximum 14 days
Overall Study Death	10	4
Overall Study Eligibility criteria not fulfilled	0	1
Overall Study Withdrawal by Subject	3	8
Overall Study Not treated	8	3
Overall Study Investigator's misjudgement	1	2

Baseline Characteristics

Stress Ulcer Prophylaxis of Intravenous Esomeprazole in Chinese Seriously Ill Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Esomeprazole n=147 Participants iv Esomeprazole 40 mg bid 30 min intermittent infusion given for maximum 14 days	Cimetidine n=153 Participants iv Cimetidine 300 mg 30 min bolus infusion, followed by iv Cimetidine continuous infusion (50 mg/h) given for maximum 14 days	Total n=300 Participants Total of all reporting groups
Age, Continuous	50.6 years STANDARD_DEVIATION 11.8 • n=99 Participants	50.1 years STANDARD_DEVIATION 12.4 • n=107 Participants	50.4 years STANDARD_DEVIATION 12.1 • n=206 Participants
Age, Customized <65 years	131 participants n=99 Participants	132 participants n=107 Participants	263 participants n=206 Participants
Age, Customized >=65 years	16 participants n=99 Participants	21 participants n=107 Participants	37 participants n=206 Participants
Sex: Female, Male Female	43 Participants n=99 Participants	38 Participants n=107 Participants	81 Participants n=206 Participants
Sex: Female, Male Male	104 Participants n=99 Participants	115 Participants n=107 Participants	219 Participants n=206 Participants
Race/Ethnicity, Customized Asian/Chinese	147 participants n=99 Participants	153 participants n=107 Participants	300 participants n=206 Participants

PRIMARY outcome

Timeframe: 1-14 days

Population: Full analysis set (FAS). All randomized patients in whom at least one dose of randomized treatment has been initiated.

Outcome measures

Outcome measures
Measure	Esomeprazole n=147 Participants iv Esomeprazole 40 mg bid 30 min intermittent infusion given for maximum 14 days	Cimetidine n=153 Participants iv Cimetidine 300 mg 30 min bolus infusion, followed by iv Cimetidine continuous infusion (50 mg/h) given for maximum 14 days
The Percent of Patients With Clinically Significant Upper-GI Bleeding During the Treatment Evaluation Phase	2.7 % of participants	4.6 % of participants

SECONDARY outcome

Timeframe: 1-14 days

Population: Full analysis set (FAS). All randomized patients in whom at least one dose of randomized treatment has been initiated.

Criteria for a significant upper GI bleeding as described in primary outcome measure or, Criteria for a non-significant upper GI bleeding as: 1. Bright red blood per NG or OG tube that clear after NG or OG tube adjustment and 5 to 10 minutes of lavage with room temperature normal saline or, 2. Persistent gastroccult- positive coffee ground material During IMP treatment Day 1-2: Persistent gastroccult - positive coffee ground material for at less than eight consecutive hours or that clear with at least 100 ml of lavage with room temperature normal saline. During IMP treatment Day 3-14: Persistent gastroccult - positive coffee ground material in less than three consecutive gastric aspirates within 2 to 4 hours (at least 60±20 minutes apart), or that clear with at least 100 ml of lavage with room temperature normal saline or, 3. Any clinical signs of hematemesis or melena or haematochezia judged (by the Investigator) to be from an upper GI source.

Outcome measures

Outcome measures
Measure	Esomeprazole n=147 Participants iv Esomeprazole 40 mg bid 30 min intermittent infusion given for maximum 14 days	Cimetidine n=153 Participants iv Cimetidine 300 mg 30 min bolus infusion, followed by iv Cimetidine continuous infusion (50 mg/h) given for maximum 14 days
Proportion of Patients With Any Overt Upper-GI Bleeding (Significant and Non-significant) During the Treatment Evaluation Phase	0.109 proportion of participants	0.105 proportion of participants

Adverse Events

Cimetidine

Serious events: 12 serious events

Other events: 88 other events

Deaths: 0 deaths

Esomeprazole

Serious events: 14 serious events

Other events: 85 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Cimetidine n=153 participants at risk iv Cimetidine 300 mg 30 min bolus infusion, followed by iv Cimetidine continuous infusion (50 mg/h) given for maximum 14 days	Esomeprazole n=147 participants at risk iv Esomeprazole 40 mg bid 30 min intermittent infusion given for maximum 14 days
Blood and lymphatic system disorders Anaemia	9.8% 15/153 • Number of events 15 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	8.8% 13/147 • Number of events 13 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Gastrointestinal disorders Constipation	9.2% 14/153 • Number of events 15 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	5.4% 8/147 • Number of events 11 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	6.5% 10/153 • Number of events 13 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	4.1% 6/147 • Number of events 7 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
General disorders Pyrexia	16.3% 25/153 • Number of events 31 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	18.4% 27/147 • Number of events 31 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Hepatobiliary disorders Hepatic function abnormal	6.5% 10/153 • Number of events 10 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	6.1% 9/147 • Number of events 9 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Infections and infestations Lung infection	20.3% 31/153 • Number of events 31 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	19.0% 28/147 • Number of events 28 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Metabolism and nutrition disorders Hyperglycaemia	5.9% 9/153 • Number of events 10 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	8.8% 13/147 • Number of events 14 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Metabolism and nutrition disorders Hypernatraemia	4.6% 7/153 • Number of events 7 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	6.1% 9/147 • Number of events 10 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Metabolism and nutrition disorders Hypokalaemia	12.4% 19/153 • Number of events 22 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	17.0% 25/147 • Number of events 28 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Metabolism and nutrition disorders Hypoproteinaemia	5.9% 9/153 • Number of events 9 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	7.5% 11/147 • Number of events 11 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Vascular disorders Hypotension	4.6% 7/153 • Number of events 7 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	5.4% 8/147 • Number of events 9 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.

Additional Information

Barry Traxler

AstraZeneca

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cimetidine n=153 participants at risk iv Cimetidine 300 mg 30 min bolus infusion, followed by iv Cimetidine continuous infusion (50 mg/h) given for maximum 14 days	Esomeprazole n=147 participants at risk iv Esomeprazole 40 mg bid 30 min intermittent infusion given for maximum 14 days
Cardiac disorders Cardio-respiratory arrest	0.00% 0/153 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	0.68% 1/147 • Number of events 1 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Cardiac disorders Cardiogenic shock	0.00% 0/153 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	0.68% 1/147 • Number of events 1 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Cardiac disorders Low cardiac output syndrome	0.00% 0/153 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	0.68% 1/147 • Number of events 1 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.65% 1/153 • Number of events 1 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	0.00% 0/147 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
General disorders Multi-organ failure	0.00% 0/153 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	1.4% 2/147 • Number of events 2 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Infections and infestations Septic shock	1.3% 2/153 • Number of events 2 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	2.0% 3/147 • Number of events 3 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Injury, poisoning and procedural complications Brain herniation	0.65% 1/153 • Number of events 1 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	0.00% 0/147 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/153 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	0.68% 1/147 • Number of events 1 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Musculoskeletal and connective tissue disorders Systemic sclerosis	0.00% 0/153 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	0.68% 1/147 • Number of events 1 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Nervous system disorders Altered state of consciousness	0.65% 1/153 • Number of events 1 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	0.00% 0/147 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Nervous system disorders Brain oedema	0.65% 1/153 • Number of events 1 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	0.00% 0/147 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Nervous system disorders Cerebral circulatory failure	0.65% 1/153 • Number of events 1 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	0.00% 0/147 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Nervous system disorders Cerebral haemorrhage	0.65% 1/153 • Number of events 1 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	1.4% 2/147 • Number of events 2 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Nervous system disorders Mental impairment	0.65% 1/153 • Number of events 1 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	0.00% 0/147 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Nervous system disorders Subarachnoid haemorrhage	0.65% 1/153 • Number of events 1 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	0.00% 0/147 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Respiratory, thoracic and mediastinal disorders Bronchial haemorrhage	0.00% 0/153 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	0.68% 1/147 • Number of events 1 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.65% 1/153 • Number of events 1 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	0.00% 0/147 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Respiratory, thoracic and mediastinal disorders Hypercapnia	0.00% 0/153 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	0.68% 1/147 • Number of events 1 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.65% 1/153 • Number of events 1 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	0.00% 0/147 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Vascular disorders Hypovolaemic shock	0.00% 0/153 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	0.68% 1/147 • Number of events 1 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.
Vascular disorders Shock haemorrhagic	0.65% 1/153 • Number of events 1 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.	0.00% 0/147 • AEs will be collected from the time of the first administration of IMP until the end of follow-up, up to 15 days. SAEs will be collected from signed inform consent until the end of follow-up, up to 15 days.