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GR270773 In The Treatment Of Suspected Or Confirmed Gram-Negative Severe Sepsis In Adults

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ClinicalTrials.gov Identifier: NCT00089986
Recruitment Status : Completed
First Posted : August 23, 2004
Results First Posted : May 4, 2017
Last Update Posted : August 21, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Primary Purpose: Treatment
Condition Sepsis
Interventions Drug: Intravenous GR270773- Phospholipid Emulsion
Other: Placebo
Enrollment 1415
Recruitment Details The study was planned on 1845 participants, hospitalized with suspected or confirmed gram-negative severe sepsis, male or female >=18 years of age at 235 centers across 31 countries from 02 September 2004 to 25 June 2007.
Pre-assignment Details A total of 1415 participant numbers were assigned during randomization process, five were duplicate randomization numbers and for other two, the participants did not provide informed consent, precluding them from enrollment. Out of 1408 participants, 29 did not receive study medication, remaining 1379 included in Intent-to-Treat (ITT) Population.
Arm/Group Title Placebo Low GR270773 High GR270773
Hide Arm/Group Description Eligible participants were administered matching placebo to low-dose GR270773 or high-dose GR270773, intravenously (IV) as a loading dose infused over 2 hours (h) followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The low placebo rate consisted of a loading dose of 0.75 milliliters per kilogram per hour (mL/kg/h) for 2 h and a maintenance dose of 0.1 mL/kg/h for 70 h. The high placebo rate consisted of a loading dose of 1.5 mL/kg/h for 2 h and a maintenance dose of 0.15 mL/kg/h for 70 h. Eligible participants were administered low-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 milligrams per milliliter (mg/mL) lipid emulsion for IV administration. The low dose emulsion consisted of a loading dose of 75 milligram (mg)/kg/h which was equivalent to 0.75 mL/kg/h for 2 h and a maintenance dose of 10 mg/kg/h which was equivalent to 0.1 mL/kg/h for 70 h. The total dose was 850 mg/kg. Eligible participants were administered high-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The high dose emulsion consisted of a loading dose of 15 mg/kg/h which was equivalent to 1.5 mL/kg/h for 2 h and a maintenance dose of 15 mg/kg/h which was equivalent to 0.15 mL/kg/h for 70 h. The total dose was 1350 mg/kg.
Period Title: Overall Study
Started 599 598 182
Completed 584 574 172
Not Completed 15 24 10
Reason Not Completed
Adverse Event             6             9             6
Lost to Follow-up             3             1             1
Protocol Violation             0             1             0
Patient transferred to another hospital             2             1             0
Subject withdrew but agreed follow up             1             2             0
Hemohlobin stopping rule             0             1             0
Investigator decision to withdrew             0             1             0
Enrollment in another study             0             1             0
Family decision             0             1             0
Do not resuscitate (DNR)             0             0             1
Withdrawal by Subject             3             6             2
Arm/Group Title Placebo Low GR270773 High GR270773 Total
Hide Arm/Group Description Eligible participants were administered matching placebo to low-dose GR270773 or high-dose GR270773, IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The low placebo rate consisted of a loading dose of 0.75 mL/kg/h for 2 h and a maintenance dose of 0.1 mL/kg/h for 70 h. The high placebo rate consisted of a loading dose of 1.5 mL/kg/h for 2 h and a maintenance dose of 0.15 mL/kg/h for 70 h. Eligible participants were administered low-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The low dose emulsion consisted of a loading dose of 75 mg/kg/h which was equivalent to 0.75 mL/kg/h for 2 h and a maintenance dose of 10 mg/kg/h which was equivalent to 0.1 mL/kg/h for 70 h. The total dose was 850 mg/kg. Eligible participants were administered high-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The high dose emulsion consisted of a loading dose of 15 mg/kg/h which was equivalent to 1.5 mL/kg/h for 2 h and a maintenance dose of 15 mg/kg/h which was equivalent to 0.15 mL/kg/h for 70 h. The total dose was 1350 mg/kg. Total of all reporting groups
Overall Number of Baseline Participants 599 598 182 1379
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 599 participants 598 participants 182 participants 1379 participants
63.1  (16.41) 62.8  (16.27) 64.8  (15.47) 63.2  (16.23)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 599 participants 598 participants 182 participants 1379 participants
Female
254
  42.4%
239
  40.0%
80
  44.0%
573
  41.6%
Male
345
  57.6%
359
  60.0%
102
  56.0%
806
  58.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 599 participants 598 participants 182 participants 1379 participants
Arabic/North African 7 6 1 14
Black 16 14 2 32
East & South East Asian 51 44 14 109
Japanese 3 3 0 6
South Asian 29 32 2 63
White/Caucasian 484 494 161 1139
Pacific Islander 1 0 0 1
American Indian 4 2 0 6
Native Hawaiian 2 0 0 2
Missing 2 3 2 7
1.Primary Outcome
Title Percentage of Participants With 28-Day All Cause Mortality
Hide Description Mortality was assessed by the number of participants who died between days 1 and 28. A summary of death details was given which included whether the participant died between days 1 and 28, whether the death was related sepsis, cause of death, the source of the information, and whether the cause of death was verified by a death record. Participants who had withdrawn from study and all study assessments and for whom survival at day 28 could not be confirmed was treated as deaths for the primary endpoint. The difference in all-cause 28-day mortality rates for each treatment group versus the placebo group in the ITT Population was calculated as placebo – treatment.
Time Frame Day 1 (post-infusion) up to Day 28 Follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population was defined as all randomized participants from all three stages who receive any study drug.
Arm/Group Title Placebo Low GR270773 High GR270773
Hide Arm/Group Description:
Eligible participants were administered matching placebo to low-dose GR270773 or high-dose GR270773, IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The low placebo rate consisted of a loading dose of 0.75 mL/kg/h for 2 h and a maintenance dose of 0.1 mL/kg/h for 70 h. The high placebo rate consisted of a loading dose of 1.5 mL/kg/h for 2 h and a maintenance dose of 0.15 mL/kg/h for 70 h.
Eligible participants were administered low-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The low dose emulsion consisted of a loading dose of 75 mg/kg/h which was equivalent to 0.75 mL/kg/h for 2 h and a maintenance dose of 10 mg/kg/h which was equivalent to 0.1 mL/kg/h for 70 h. The total dose was 850 mg/kg.
Eligible participants were administered high-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The high dose emulsion consisted of a loading dose of 15 mg/kg/h which was equivalent to 1.5 mL/kg/h for 2 h and a maintenance dose of 15 mg/kg/h which was equivalent to 0.15 mL/kg/h for 70 h. The total dose was 1350 mg/kg.
Overall Number of Participants Analyzed 599 598 182
Measure Type: Number
Unit of Measure: Percentage of participants
26.9 25.8 31.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Low GR270773
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.329
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate difference
Estimated Value 1.1
Confidence Interval (1-Sided) 90%
-2.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, High GR270773
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.879
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Difference
Estimated Value -4.4
Confidence Interval (1-Sided) 90%
-9.4
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants With New Onset Organ Failure, Regardless of Cause, Occurring During the 28 Days Post Enrollment in an Organ Not in Failure at Enrolment
Hide Description The new onset organ failure was defined as first time each of the following criteria were met after start of study medication up to Day 28. Respiratory failure: defined by requiring mechanical ventilation not less than 24 hours due to surgery. Renal failure: defined by requiring the initiation of hemodialysis or hemofiltration. Coagulopathy: defined by disseminated intravascular coagulation (DIC) requiring transfusion with platelets or fresh frozen plasma or anticoagulant therapy. Cardiovascular failure: defined by sustained hypotension requiring vasopressor support of dopamine >5 microgram per kilogram per minute (µg/kg/min), epinephrine, norepinephrine, phenylephrine or vasopressin at any dose if used to increase blood pressure for >=6 continuous h. Analysis was done treating the death as a new onset organ failure (counted in both the numerator and denominator).
Time Frame Baseline (Day 1, pre-infusion) up to Day 28 Follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Organ failure occurring during the 28 days post-enrollment that was not in failure at enrollment. Subjects who die prior to observing a new organ failure are counted as a failure.
Arm/Group Title Placebo Low GR270773 High GR270773
Hide Arm/Group Description:
Eligible participants were administered matching placebo to low-dose GR270773 or high-dose GR270773, IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The low placebo rate consisted of a loading dose of 0.75 mL/kg/h for 2 h and a maintenance dose of 0.1 mL/kg/h for 70 h. The high placebo rate consisted of a loading dose of 1.5 mL/kg/h for 2 h and a maintenance dose of 0.15 mL/kg/h for 70 h.
Eligible participants were administered low-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The low dose emulsion consisted of a loading dose of 75 mg/kg/h which was equivalent to 0.75 mL/kg/h for 2 h and a maintenance dose of 10 mg/kg/h which was equivalent to 0.1 mL/kg/h for 70 h. The total dose was 850 mg/kg.
Eligible participants were administered high-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The high dose emulsion consisted of a loading dose of 15 mg/kg/h which was equivalent to 1.5 mL/kg/h for 2 h and a maintenance dose of 15 mg/kg/h which was equivalent to 0.15 mL/kg/h for 70 h. The total dose was 1350 mg/kg.
Overall Number of Participants Analyzed 599 598 182
Measure Type: Count of Participants
Unit of Measure: Participants
122
  20.4%
157
  26.3%
57
  31.3%
3.Secondary Outcome
Title Number of Participants With New Onset Organ Failure of Respiratory Failure, Cardiovascular Failure, Renal Failure and Coagulopathy, Regardless of Cause, Occurring During the 28 Days Post Enrollment in an Organ Not in Failure at Enrollment
Hide Description Respiratory failure: defined by requiring mechanical ventilation not less than 24 hours due to surgery. Renal failure: defined by requiring the initiation of hemodialysis or hemofiltration. Coagulopathy: defined by disseminated intravascular coagulation (DIC) requiring transfusion with platelets or fresh frozen plasma or anticoagulant therapy. Cardiovascular failure: defined by sustained hypotension requiring vasopressor support of dopamine >5 microgram per kilogram per minute (µg/kg/min), epinephrine, norepinephrine, phenylephrine or vasopressin at any dose if used to increase blood pressure for >=6 continuous h. For each organ failure type and the number of new onset organ failures per participants for each organ failure type, the denominator only included participants who did not have that type of organ failure at Baseline. At Baseline a participant could enter the study with a type of organ failure, that type of failure was not reported as a new onset organ failure.
Time Frame Baseline (Day 1, pre-infusion) up to Day 28 Follow up
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Organ failure occurring during the 28 days post-enrollment that was not in failure at enrollment. Participants who died prior to observing a new failure are excluded from analysis.
Arm/Group Title Placebo Low GR270773 High GR270773
Hide Arm/Group Description:
Eligible participants were administered matching placebo to low-dose GR270773 or high-dose GR270773, IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The low placebo rate consisted of a loading dose of 0.75 mL/kg/h for 2 h and a maintenance dose of 0.1 mL/kg/h for 70 h. The high placebo rate consisted of a loading dose of 1.5 mL/kg/h for 2 h and a maintenance dose of 0.15 mL/kg/h for 70 h.
Eligible participants were administered low-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The low dose emulsion consisted of a loading dose of 75 mg/kg/h which was equivalent to 0.75 mL/kg/h for 2 h and a maintenance dose of 10 mg/kg/h which was equivalent to 0.1 mL/kg/h for 70 h. The total dose was 850 mg/kg.
Eligible participants were administered high-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The high dose emulsion consisted of a loading dose of 15 mg/kg/h which was equivalent to 1.5 mL/kg/h for 2 h and a maintenance dose of 15 mg/kg/h which was equivalent to 0.15 mL/kg/h for 70 h. The total dose was 1350 mg/kg.
Overall Number of Participants Analyzed 599 598 182
Measure Type: Count of Participants
Unit of Measure: Participants
Respiratory failure, n= 297, 333, 99
50
   8.3%
61
  10.2%
23
  12.6%
Cardiovascular failure, n= 150, 161, 43
33
   5.5%
48
   8.0%
15
   8.2%
Renal failure, n= 460, 474, 138
40
   6.7%
47
   7.9%
22
  12.1%
Coagulopathy, n= 344, 355, 107
36
   6.0%
41
   6.9%
16
   8.8%
4.Secondary Outcome
Title Assessment of Safety/Tolerability by Determining the Number of Participants With Any Adverse Events (AE), Serious Adverse Events (SAE) and Fatal SAE
Hide Description An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition or common toxicity criteria (CTC) grade 4 laboratory abnormalities of national cancer institute not associated with the underlying sepsis unless more severe than expected for the participants condition.
Time Frame Day 1 (pre-infusion) up to Day 28 Follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Placebo Low GR270773 High GR270773
Hide Arm/Group Description:
Eligible participants were administered matching placebo to low-dose GR270773 or high-dose GR270773, IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The low placebo rate consisted of a loading dose of 0.75 mL/kg/h for 2 h and a maintenance dose of 0.1 mL/kg/h for 70 h. The high placebo rate consisted of a loading dose of 1.5 mL/kg/h for 2 h and a maintenance dose of 0.15 mL/kg/h for 70 h.
Eligible participants were administered low-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The low dose emulsion consisted of a loading dose of 75 mg/kg/h which was equivalent to 0.75 mL/kg/h for 2 h and a maintenance dose of 10 mg/kg/h which was equivalent to 0.1 mL/kg/h for 70 h. The total dose was 850 mg/kg.
Eligible participants were administered high-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The high dose emulsion consisted of a loading dose of 15 mg/kg/h which was equivalent to 1.5 mL/kg/h for 2 h and a maintenance dose of 15 mg/kg/h which was equivalent to 0.15 mL/kg/h for 70 h. The total dose was 1350 mg/kg.
Overall Number of Participants Analyzed 599 598 182
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
423
  70.6%
442
  73.9%
144
  79.1%
Any SAE
213
  35.6%
235
  39.3%
77
  42.3%
Any fatal SAE
85
  14.2%
70
  11.7%
33
  18.1%
Time Frame AE and SAE were collected from Baseline (Day 1, pre-infusion) to Day 28 Follow-up
Adverse Event Reporting Description ITT Population was used which was defined as all randomized participants from all three stages who receive any study drug.
 
Arm/Group Title Placebo Low GR270773 High GR270773
Hide Arm/Group Description Eligible participants were administered matching placebo to low-dose GR270773 or high-dose GR270773, IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The low placebo rate consisted of a loading dose of 0.75 mL/kg/h for 2 h and a maintenance dose of 0.1 mL/kg/h for 70 h. The high placebo rate consisted of a loading dose of 1.5 mL/kg/h for 2 h and a maintenance dose of 0.15 mL/kg/h for 70 h. Eligible participants were administered low-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The low dose emulsion consisted of a loading dose of 75 mg/kg/h which was equivalent to 0.75 mL/kg/h for 2 h and a maintenance dose of 10 mg/kg/h which was equivalent to 0.1 mL/kg/h for 70 h. The total dose was 850 mg/kg. Eligible participants were administered high-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The high dose emulsion consisted of a loading dose of 15 mg/kg/h which was equivalent to 1.5 mL/kg/h for 2 h and a maintenance dose of 15 mg/kg/h which was equivalent to 0.15 mL/kg/h for 70 h. The total dose was 1350 mg/kg.
All-Cause Mortality
Placebo Low GR270773 High GR270773
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   85/599 (14.19%)   70/598 (11.71%)   33/182 (18.13%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Low GR270773 High GR270773
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   213/599 (35.56%)   235/598 (39.30%)   77/182 (42.31%) 
Blood and lymphatic system disorders       
Anaemia  2  3/599 (0.50%)  8/598 (1.34%)  1/182 (0.55%) 
Thrombocytopenia  2  6/599 (1.00%)  2/598 (0.33%)  0/182 (0.00%) 
Coombs negative haemolytic anaemia  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Haemoglobinaemia  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Haemolysis  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Leukocytosis  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Leukopenia  2  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Lymphopenia  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Red blood cell abnormality  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Thrombocytopenic purpura  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Cardiac disorders       
Cardiac arrest  1  46/599 (7.68%)  42/598 (7.02%)  17/182 (9.34%) 
Atrial fibrillation  1  3/599 (0.50%)  6/598 (1.00%)  1/182 (0.55%) 
Myocardial infarction  1  4/599 (0.67%)  1/598 (0.17%)  2/182 (1.10%) 
Acute myocardial infarction  1  0/599 (0.00%)  3/598 (0.50%)  3/182 (1.65%) 
Ventricular tachycardia  1  4/599 (0.67%)  0/598 (0.00%)  1/182 (0.55%) 
Cardiac failure  1  2/599 (0.33%)  1/598 (0.17%)  1/182 (0.55%) 
Bradycardia  1  0/599 (0.00%)  3/598 (0.50%)  0/182 (0.00%) 
Ventricular fibrillation  1  1/599 (0.17%)  2/598 (0.33%)  0/182 (0.00%) 
Cardiac failure acute  1  0/599 (0.00%)  2/598 (0.33%)  0/182 (0.00%) 
Cardiac failure congestive  1  1/599 (0.17%)  1/598 (0.17%)  0/182 (0.00%) 
Tachyarrhythmia  1  0/599 (0.00%)  2/598 (0.33%)  0/182 (0.00%) 
Torsade de pointes  1  0/599 (0.00%)  1/598 (0.17%)  1/182 (0.55%) 
Angina pectoris  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Arrhythmia  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Bradyarrhythmia  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Cardio-respiratory arrest  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Cardiogenic shock  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Electromechanical dissociation  1  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Left ventricular failure  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Nodal arrhythmia  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Supraventricular tachyarrhythmia  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Supraventricular tachycardia  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Ventricular tachyarrhythmia  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Gastrointestinal disorders       
Gastrointestinal haemorrhage  1  3/599 (0.50%)  4/598 (0.67%)  0/182 (0.00%) 
Pancreatitis  1  1/599 (0.17%)  3/598 (0.50%)  0/182 (0.00%) 
Intestinal ischaemia  1  2/599 (0.33%)  1/598 (0.17%)  0/182 (0.00%) 
Pancreatitis acute  1  2/599 (0.33%)  1/598 (0.17%)  0/182 (0.00%) 
Rectal haemorrhage  1  2/599 (0.33%)  1/598 (0.17%)  0/182 (0.00%) 
Upper gastrointestinal haemorrhage  1  2/599 (0.33%)  1/598 (0.17%)  0/182 (0.00%) 
Ileus paralytic  1  1/599 (0.17%)  1/598 (0.17%)  0/182 (0.00%) 
Intestinal obstruction  1  1/599 (0.17%)  1/598 (0.17%)  0/182 (0.00%) 
Intra-abdominal haemorrhage  1  0/599 (0.00%)  1/598 (0.17%)  1/182 (0.55%) 
Abdominal hernia  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Abdominal pain  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Acute abdomen  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Duodenal perforation  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Duodenal ulcer perforation  1  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Gastric ulcer haemorrhage  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Haematochezia  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Intestinal perforation  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Lower gastrointestinal haemorrhage  1  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Mesenteric artery thrombosis  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Oesophageal rupture  1  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Pancreatic duct obstruction  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Pancreatitis necrotising  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Peritoneal haemorrhage  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Peritoneal necrosis  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Peritonitis  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Retroperitoneal haematoma  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Retroperitoneal haemorrhage  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Small intestinal haemorrhage  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Large intestine perforation  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
General disorders       
Multi-organ failure  2  3/599 (0.50%)  1/598 (0.17%)  1/182 (0.55%) 
Pyrexia  2  2/599 (0.33%)  1/598 (0.17%)  1/182 (0.55%) 
Cardiac death  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
General physical health deterioration  2  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Hyperpyrexia  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Multi-organ disorder  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Sudden cardiac death  2  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Hepatobiliary disorders       
Hepatic failure  1  20/599 (3.34%)  25/598 (4.18%)  15/182 (8.24%) 
Cholangitis  1  1/599 (0.17%)  2/598 (0.33%)  0/182 (0.00%) 
Hyperbilirubinaemia  1  2/599 (0.33%)  1/598 (0.17%)  0/182 (0.00%) 
Bile duct stone  1  0/599 (0.00%)  2/598 (0.33%)  0/182 (0.00%) 
Cholestasis  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Cytolytic hepatitis  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Hepatic function abnormal  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Hydrocholecystis  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Ischaemic hepatitis  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Jaundice  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Liver disorder  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Cholecystitis  2  1/599 (0.17%)  1/598 (0.17%)  1/182 (0.55%) 
Immune system disorders       
Hypersensitivity  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Infections and infestations       
Pneumonia  1  5/599 (0.83%)  2/598 (0.33%)  2/182 (1.10%) 
Septic shock  1  6/599 (1.00%)  2/598 (0.33%)  0/182 (0.00%) 
Sepsis  1  1/599 (0.17%)  2/598 (0.33%)  1/182 (0.55%) 
Urinary tract infection  1  3/599 (0.50%)  0/598 (0.00%)  0/182 (0.00%) 
Abdominal abscess  1  0/599 (0.00%)  2/598 (0.33%)  0/182 (0.00%) 
Bacteraemia  1  1/599 (0.17%)  0/598 (0.00%)  1/182 (0.55%) 
Pyelonephritis  1  1/599 (0.17%)  0/598 (0.00%)  1/182 (0.55%) 
Wound infection  1  1/599 (0.17%)  1/598 (0.17%)  0/182 (0.00%) 
Brain abscess  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Bronchitis  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Bronchopneumonia  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Citrobacter sepsis  1  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Colitis pseudomembranous  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Endocarditis bacterial  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Extradural abscess  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Fungaemia  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Infected skin ulcer  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Lobar pneumonia  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Localised infection  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Lower respiratory tract infection  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Necrotising fasciitis  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Perinephric abscess  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Postoperative wound infection  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Injury, poisoning and procedural complications       
Heart injury  2  3/599 (0.50%)  1/598 (0.17%)  0/182 (0.00%) 
Wound dehiscence  2  2/599 (0.33%)  2/598 (0.33%)  0/182 (0.00%) 
Graft complication  2  1/599 (0.17%)  1/598 (0.17%)  0/182 (0.00%) 
Wound evisceration  2  0/599 (0.00%)  2/598 (0.33%)  0/182 (0.00%) 
Anastomotic leak  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Failure to anastomose  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Post procedural bile leak  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Post procedural haemorrhage  2  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Splenic rupture  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Tracheal haemorrhage  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Investigations       
Lipase increased  1  7/599 (1.17%)  10/598 (1.67%)  1/182 (0.55%) 
Gamma-glutamyltransferase increased  1  4/599 (0.67%)  3/598 (0.50%)  0/182 (0.00%) 
Haemoglobin decreased  1  2/599 (0.33%)  2/598 (0.33%)  0/182 (0.00%) 
Hepatic enzyme increased  1  3/599 (0.50%)  1/598 (0.17%)  0/182 (0.00%) 
Aspartate aminotransferase increased  1  1/599 (0.17%)  2/598 (0.33%)  0/182 (0.00%) 
Blood amylase increased  1  1/599 (0.17%)  1/598 (0.17%)  1/182 (0.55%) 
Alanine aminotransferase increased  1  1/599 (0.17%)  1/598 (0.17%)  0/182 (0.00%) 
Carbon dioxide decreased  1  2/599 (0.33%)  0/598 (0.00%)  0/182 (0.00%) 
Blood bilirubin increased  1  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Blood creatinine increased  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Cardiac output decreased  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Haematocrit decreased  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Myelocyte present  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Pancreatic enzymes increased  1  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Platelet count decreased  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Transaminases increased  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Troponin increased  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Metabolism and nutrition disorders       
Metabolic acidosis  1  49/599 (8.18%)  61/598 (10.20%)  23/182 (12.64%) 
Hypoglycaemia  1  4/599 (0.67%)  10/598 (1.67%)  2/182 (1.10%) 
Hypokalaemia  1  7/599 (1.17%)  1/598 (0.17%)  0/182 (0.00%) 
Hyperkalaemia  1  2/599 (0.33%)  3/598 (0.50%)  0/182 (0.00%) 
Hyperamylasaemia  1  1/599 (0.17%)  3/598 (0.50%)  0/182 (0.00%) 
Hyperglycaemia  1  1/599 (0.17%)  2/598 (0.33%)  0/182 (0.00%) 
Hypernatraemia  1  2/599 (0.33%)  1/598 (0.17%)  0/182 (0.00%) 
Dehydration  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Hyperuricaemia  1  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Hyponatraemia  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Shock hypoglycaemic  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Musculoskeletal and connective tissue disorders       
Muscle necrosis  2  2/599 (0.33%)  0/598 (0.00%)  0/182 (0.00%) 
Arthralgia  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Pain in extremity  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Myelodysplastic syndrome  2  1/599 (0.17%)  1/598 (0.17%)  1/182 (0.55%) 
Bile duct cancer  2  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Metastases to central nervous system  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Metastases to liver  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Non-Hodgkin’s lymphoma  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Salivary gland neoplasm  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Transitional cell carcinoma  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Nervous system disorders       
Mental impairment  1  38/599 (6.34%)  38/598 (6.35%)  12/182 (6.59%) 
Cerebrovascular accident  1  2/599 (0.33%)  2/598 (0.33%)  1/182 (0.55%) 
Brain oedema  1  1/599 (0.17%)  2/598 (0.33%)  1/182 (0.55%) 
Anoxic encephalopathy  1  1/599 (0.17%)  1/598 (0.17%)  0/182 (0.00%) 
Cerebral infarction  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Cerebral ischaemia  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Coma  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Dizziness  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Dizziness postural  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Encephalitis  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Encephalopathy  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Guillain-Barre syndrome  1  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Hepatic encephalopathy  1  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Hypoxic encephalopathy  1  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Ischaemic stroke  1  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Transient ischaemic attack  1  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Psychiatric disorders       
Mental status changes  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Renal and urinary disorders       
Renal failure  2  1/599 (0.17%)  1/598 (0.17%)  0/182 (0.00%) 
Renal failure acute  2  1/599 (0.17%)  1/598 (0.17%)  0/182 (0.00%) 
Bladder distension  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Haematuria  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Hydronephrosis  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Respiratory failure  2  1/599 (0.17%)  9/598 (1.51%)  1/182 (0.55%) 
Pulmonary embolism  2  3/599 (0.50%)  3/598 (0.50%)  0/182 (0.00%) 
Respiratory distress  2  3/599 (0.50%)  1/598 (0.17%)  1/182 (0.55%) 
Pneumothorax  2  1/599 (0.17%)  0/598 (0.00%)  2/182 (1.10%) 
Respiratory arrest  2  0/599 (0.00%)  2/598 (0.33%)  1/182 (0.55%) 
Acute pulmonary oedema  2  0/599 (0.00%)  1/598 (0.17%)  1/182 (0.55%) 
Hypoxia  2  0/599 (0.00%)  1/598 (0.17%)  1/182 (0.55%) 
Pulmonary oedema  2  1/599 (0.17%)  0/598 (0.00%)  1/182 (0.55%) 
Acute respiratory failure  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Aspiration  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Asthma  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Atelectasis  2  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Chronic obstructive pulmonary disease  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Haemopneumothorax  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Hypercapnia  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Hypoventilation  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Pneumonia aspiration  2  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Tachypnoea  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Thoracic haemorrhage  2  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Skin and subcutaneous tissue disorders       
Decubitus ulcer  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Vascular disorders       
Haemorrhage  2  0/599 (0.00%)  2/598 (0.33%)  3/182 (1.65%) 
Deep vein thrombosis  2  2/599 (0.33%)  2/598 (0.33%)  0/182 (0.00%) 
Shock haemorrhagic  2  3/599 (0.50%)  0/598 (0.00%)  1/182 (0.55%) 
Hypotension  2  0/599 (0.00%)  2/598 (0.33%)  0/182 (0.00%) 
Hypovolaemic shock  2  0/599 (0.00%)  1/598 (0.17%)  1/182 (0.55%) 
Aortic aneurysm rupture  2  0/599 (0.00%)  0/598 (0.00%)  1/182 (0.55%) 
Extremity necrosis  2  1/599 (0.17%)  0/598 (0.00%)  0/182 (0.00%) 
Jugular vein thrombosis  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
Shock  2  0/599 (0.00%)  1/598 (0.17%)  0/182 (0.00%) 
1
Term from vocabulary, MedDRA
2
Term from vocabulary, MedDRA 9.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Low GR270773 High GR270773
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   160/599 (26.71%)   183/598 (30.60%)   60/182 (32.97%) 
Blood and lymphatic system disorders       
Anaemia  1  76/599 (12.69%)  87/598 (14.55%)  28/182 (15.38%) 
Cardiac disorders       
Atrial fibrillation  1  44/599 (7.35%)  41/598 (6.86%)  10/182 (5.49%) 
Gastrointestinal disorders       
Diarrhoea  1  33/599 (5.51%)  50/598 (8.36%)  28/182 (15.38%) 
Nausea  1  25/599 (4.17%)  31/598 (5.18%)  15/182 (8.24%) 
Metabolism and nutrition disorders       
Hypokalaemia  1  51/599 (8.51%)  53/598 (8.86%)  16/182 (8.79%) 
1
Term from vocabulary, MedDRA 9.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
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Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00089986     History of Changes
Other Study ID Numbers: EMD20001
First Submitted: August 18, 2004
First Posted: August 23, 2004
Results First Submitted: March 23, 2017
Results First Posted: May 4, 2017
Last Update Posted: August 21, 2017