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Prevention of Invasive Fungal Infections (IFIs) in Subjects Receiving Chemotherapy for Acute Lymphoblastic Leukemia (AmBiGuard)

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ClinicalTrials.gov Identifier: NCT01259713
Recruitment Status : Completed
First Posted : December 14, 2010
Results First Posted : April 6, 2015
Last Update Posted : May 7, 2015
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Invasive Fungal Disease
Interventions Drug: Liposomal amphotericin B
Drug: Placebo
Enrollment 355
Recruitment Details Participants were enrolled at a total of 86 study sites. The first participant was screened on 13 April 2011. The last study visit occurred on 29 January 2014.
Pre-assignment Details 391 participants were screened.
Arm/Group Title Liposomal Amphotericin B Placebo
Hide Arm/Group Description Liposomal amphotericin B (AmBisome®) 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy Placebo to match liposomal amphotericin B twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
Period Title: Overall Study
Started 237 118
Completed 142 77
Not Completed 95 41
Reason Not Completed
Adverse Event             54             23
Death Not Related to IFI             8             1
Investigators Discretion             14             6
Lack of Efficacy             2             0
Protocol Violation             5             4
Subject Withdrew Consent             12             7
Arm/Group Title Liposomal Amphotericin B Placebo Total
Hide Arm/Group Description Liposomal amphotericin B 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy Placebo to match liposomal amphotericin B twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy Total of all reporting groups
Overall Number of Baseline Participants 237 118 355
Hide Baseline Analysis Population Description
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 237 participants 118 participants 355 participants
44.5  (15.16) 44.8  (17.52) 44.6  (15.96)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 237 participants 118 participants 355 participants
≤ 25 years 37 25 62
> 25 to ≤ 60 years 160 64 224
> 60 years 40 29 69
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 237 participants 118 participants 355 participants
Female
98
  41.4%
58
  49.2%
156
  43.9%
Male
139
  58.6%
60
  50.8%
199
  56.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 237 participants 118 participants 355 participants
Asian 1 0 1
Black 4 3 7
White 211 100 311
Not Permitted 17 15 32
Other 4 0 4
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 237 participants 118 participants 355 participants
Germany 52 23 75
Italy 41 25 66
France 33 19 52
Belgium 20 11 31
Spain 21 7 28
Greece 14 13 27
Portugal 13 4 17
Turkey 7 4 11
Austria 6 3 9
Israel 9 0 9
Switzerland 6 1 7
Brazil 8 7 15
Argentina 7 1 8
1.Primary Outcome
Title Percentage of Participants With Proven or Probable IFIs During Remission-induction Chemotherapy for Acute Lymphoblastic Leukemia (ALL)
Hide Description

Diagnoses of proven or probable invasive fungal infections (IFI) were assessed according to European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria by the independent data review board (IDRB) who were blinded to treatment assignment.

The duration of remission-induction chemotherapy was defined as the period from the initiation of remission-induction chemotherapy administration to the start of consolidation or salvage therapy.

Time Frame During remission-induction chemotherapy (average 7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Analysis Set: participants in the safety analysis set who had no major violations of entrance criteria.
Arm/Group Title Liposomal Amphotericin B Placebo
Hide Arm/Group Description:
Liposomal amphotericin B 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
Placebo to match liposomal amphotericin B twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
Overall Number of Participants Analyzed 228 111
Measure Type: Number
Unit of Measure: percentage of participants
7.9 11.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Liposomal Amphotericin B, Placebo
Comments A two-group Cochran-Mantel-Haenszel (CMH) test with a 0.05 two-sided significance level and 2:1 allocation of 354 randomized subjects (236 AmBisome, 118 placebo) would have 81% power to detect a relative reduction of 75% if the rate of IFI is 10% in the placebo group (based on unpublished data from the German Multicenter Acute Lymphoblastic Leukemia Working Group (GMALL) and consistent with the published rate of 16.4% in patients with hematological malignancies undergoing remission induction).
Type of Statistical Test Non-Inferiority or Equivalence
Comments For the interim analysis performed when 50% of the subjects had completed the study, an alpha of 0.0003 was spent. Therefore, the significance level for the 2-sided test in the primary analysis at the end of the study was 0.0497 (corresponding to 95.03% confidence interval (CI)).
Statistical Test of Hypothesis P-Value 0.24
Comments P-value was from a stratum-adjusted (stratified by region) CMH test.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative risk reduction
Estimated Value 0.33
Confidence Interval (2-Sided) 95.03%
-0.32 to 0.66
Estimation Comments Relative risk reduction = 1 - risk ratio.
2.Secondary Outcome
Title Percentage of Participants With Pulmonary Infiltrates According to the Central Image Reader
Hide Description [Not Specified]
Time Frame During remission-induction chemotherapy (average 7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title Liposomal Amphotericin B Placebo
Hide Arm/Group Description:
Liposomal amphotericin B 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
Placebo to match liposomal amphotericin B twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
Overall Number of Participants Analyzed 228 111
Measure Type: Number
Unit of Measure: percentage of participants
20.2 27.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Liposomal Amphotericin B, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments P-value was from a stratum-adjusted (stratified by region) CMH test.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative risk reduction
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
-0.11 to 0.50
Estimation Comments Relative risk reduction = 1 - risk ratio.
3.Secondary Outcome
Title Percentage of Participants Diagnosed With Proven or Probable IFIs According to the EORTC/MSG Criteria, as Assessed by the Investigator
Hide Description [Not Specified]
Time Frame During remission-induction chemotherapy (average 7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title Liposomal Amphotericin B Placebo
Hide Arm/Group Description:
Liposomal amphotericin B 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
Placebo to match liposomal amphotericin B twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
Overall Number of Participants Analyzed 228 111
Measure Type: Number
Unit of Measure: percentage of participants
11.0 10.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Liposomal Amphotericin B, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.97
Comments P-value was from a stratum-adjusted (stratified by region) CMH test.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative risk reduction
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.94 to 0.47
Estimation Comments Relative risk reduction = 1 - risk ratio.
4.Secondary Outcome
Title Time to Diagnosis of Proven or Probable IFIs According to the EORTC/MSG Criteria, as Assessed by the IDRB.
Hide Description Time to diagnosis of proven or probable IFIs is presented as the median (Q1,Q3) days to diagnosis of those participants who experienced a proven or probable IFI. Median was not reached if < 50% of participants had an event; Q1 was not reached if < 25% of participants had an event; Q3 was not reached if < 75% of participants had an event.
Time Frame During remission-induction chemotherapy (average 7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title Liposomal Amphotericin B Placebo
Hide Arm/Group Description:
Liposomal amphotericin B 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
Placebo to match liposomal amphotericin B twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
Overall Number of Participants Analyzed 228 111
Median (Inter-Quartile Range)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
NA = Not reached
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Liposomal Amphotericin B, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.33
Comments The p-value is from the log-rank test stratified by region.
Method Log Rank
Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants Requiring Antifungal Treatment During Remission-Induction Chemotherapy
Hide Description [Not Specified]
Time Frame During remission-induction chemotherapy (average 7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title Liposomal Amphotericin B Placebo
Hide Arm/Group Description:
Liposomal amphotericin B 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
Placebo to match liposomal amphotericin B twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
Overall Number of Participants Analyzed 228 111
Measure Type: Number
Unit of Measure: percentage of participants
16.2 21.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Liposomal Amphotericin B, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments P-value was from a stratum-adjusted (stratified by region) CMH test.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative risk reduction
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
-0.19 to 0.53
Estimation Comments Relative risk reduction = 1 - risk ratio.
6.Secondary Outcome
Title Percentage of Participants Who Died Due to Fungal Infection; Causality as Assessed by the IDRB.
Hide Description [Not Specified]
Time Frame During remission-induction chemotherapy (average 7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title Liposomal Amphotericin B Placebo
Hide Arm/Group Description:
Liposomal amphotericin B 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
Placebo to match liposomal amphotericin B twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
Overall Number of Participants Analyzed 228 111
Measure Type: Number
Unit of Measure: percentage of participants
0.9 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Liposomal Amphotericin B, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.32
Comments P-value was from a stratum-adjusted (stratified by region) CMH test.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants Who Died Due to Fungal Infection; Causality as Assessed by the Investigator.
Hide Description [Not Specified]
Time Frame During remission-induction chemotherapy (average 7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title Liposomal Amphotericin B Placebo
Hide Arm/Group Description:
Liposomal amphotericin B 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
Placebo to match liposomal amphotericin B twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
Overall Number of Participants Analyzed 228 111
Measure Type: Number
Unit of Measure: percentage of participants
0.9 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Liposomal Amphotericin B, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.32
Comments P-value was from a stratum-adjusted (stratified by region) CMH test.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
8.Secondary Outcome
Title Time From Beginning of Remission-induction Chemotherapy Until the Beginning of Consolidation Therapy
Hide Description This endpoint was to evaluate the potential impact of IFI prevention on the efficacy of remission-induction chemotherapy for ALL.
Time Frame During remission-induction chemotherapy (average 7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title Liposomal Amphotericin B Placebo
Hide Arm/Group Description:
Liposomal amphotericin B 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
Placebo to match liposomal amphotericin B twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
Overall Number of Participants Analyzed 228 111
Median (Inter-Quartile Range)
Unit of Measure: days
50
(38 to 75)
55
(36 to 75)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Liposomal Amphotericin B, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.69
Comments The p-value was from the log-rank test stratified by region.
Method Log Rank
Comments Participants without consolidation/salvage therapy dates were censored using the earlier of the Early Termination and Study Completion dates.
9.Secondary Outcome
Title Percentage of Participants With Complete Remission at the End of Remission Induction
Hide Description This endpoint was to evaluate the potential impact of IFI prevention on the efficacy of remission-induction chemotherapy for ALL.
Time Frame During remission-induction chemotherapy (average 7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title Liposomal Amphotericin B Placebo
Hide Arm/Group Description:
Liposomal amphotericin B 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
Placebo to match liposomal amphotericin B twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
Overall Number of Participants Analyzed 228 111
Measure Type: Number
Unit of Measure: percentage of participants
72.8 79.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Liposomal Amphotericin B, Placebo
Comments Participants were not stratified for leukemia risk.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.20
Comments P-value was from a stratum-adjusted (stratified by region) CMH test.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative risk reduction
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-0.04 to 0.19
Estimation Comments Relative risk reduction = 1 - risk ratio.
Time Frame From first dose to last dose of study drug plus 30 days.
Adverse Event Reporting Description

Safety Analysis Set; participants who were randomized and received at least 1 dose of study drug.

The duration of remission-induction chemotherapy was defined as the period from the initiation of remission-induction chemotherapy administration to the start of consolidation or salvage therapy.

 
Arm/Group Title Liposomal Amphotericin B Placebo
Hide Arm/Group Description Liposomal amphotericin B 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy Placebo to match liposomal amphotericin B twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy
All-Cause Mortality
Liposomal Amphotericin B Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Liposomal Amphotericin B Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   79/237 (33.33%)   38/118 (32.20%) 
Blood and lymphatic system disorders     
Febrile neutropenia  1  10/237 (4.22%)  6/118 (5.08%) 
Thrombocytopenia  1  2/237 (0.84%)  0/118 (0.00%) 
Anaemia  1  1/237 (0.42%)  0/118 (0.00%) 
Neutropenia  1  1/237 (0.42%)  0/118 (0.00%) 
Pancytopenia  1  1/237 (0.42%)  0/118 (0.00%) 
Cardiac disorders     
Cardiac arrest  1  4/237 (1.69%)  0/118 (0.00%) 
Arrhythmia  1  0/237 (0.00%)  1/118 (0.85%) 
Atrial fibrillation  1  0/237 (0.00%)  1/118 (0.85%) 
Cardio-respiratory arrest  1  1/237 (0.42%)  0/118 (0.00%) 
Eye disorders     
Visual acuity reduced  1  0/237 (0.00%)  1/118 (0.85%) 
Gastrointestinal disorders     
Colitis  1  1/237 (0.42%)  1/118 (0.85%) 
Pancreatitis  1  2/237 (0.84%)  0/118 (0.00%) 
Caecitis  1  1/237 (0.42%)  0/118 (0.00%) 
Ileitis  1  0/237 (0.00%)  1/118 (0.85%) 
Ileus  1  1/237 (0.42%)  0/118 (0.00%) 
Intestinal obstruction  1  1/237 (0.42%)  0/118 (0.00%) 
Intra-abdominal haemorrhage  1  0/237 (0.00%)  1/118 (0.85%) 
Upper gastrointestinal haemorrhage  1  1/237 (0.42%)  0/118 (0.00%) 
Vomiting  1  1/237 (0.42%)  0/118 (0.00%) 
General disorders     
Pyrexia  1  2/237 (0.84%)  3/118 (2.54%) 
Systemic inflammatory response syndrome  1  0/237 (0.00%)  2/118 (1.69%) 
Chestpain  1  1/237 (0.42%)  0/118 (0.00%) 
Chills  1  1/237 (0.42%)  0/118 (0.00%) 
Inflammation  1  0/237 (0.00%)  1/118 (0.85%) 
Mucosal inflammation  1  1/237 (0.42%)  0/118 (0.00%) 
Multi-organ failure  1  1/237 (0.42%)  0/118 (0.00%) 
Hepatobiliary disorders     
Hepatic failure  1  2/237 (0.84%)  0/118 (0.00%) 
Bile duct stone  1  1/237 (0.42%)  0/118 (0.00%) 
Cholecystitis  1  1/237 (0.42%)  0/118 (0.00%) 
Cholecystitis acute  1  1/237 (0.42%)  0/118 (0.00%) 
Hepatic steatosis  1  1/237 (0.42%)  0/118 (0.00%) 
Hepatocellular injury  1  1/237 (0.42%)  0/118 (0.00%) 
Hyperbilirubinaemia  1  1/237 (0.42%)  0/118 (0.00%) 
Liver disorder  1  1/237 (0.42%)  0/118 (0.00%) 
Immune system disorders     
Allergic oedema  1  1/237 (0.42%)  0/118 (0.00%) 
Drug hypersensitivity  1  1/237 (0.42%)  0/118 (0.00%) 
Hypersensitivity  1  1/237 (0.42%)  0/118 (0.00%) 
Infections and infestations     
Septic shock  1  13/237 (5.49%)  2/118 (1.69%) 
Pneumonia  1  7/237 (2.95%)  3/118 (2.54%) 
Sepsis  1  4/237 (1.69%)  6/118 (5.08%) 
Device related infection  1  3/237 (1.27%)  0/118 (0.00%) 
Bacterial sepsis  1  2/237 (0.84%)  0/118 (0.00%) 
Escherichia sepsis  1  0/237 (0.00%)  2/118 (1.69%) 
Pneumonia bacterial  1  2/237 (0.84%)  0/118 (0.00%) 
Pseudomonal sepsis  1  2/237 (0.84%)  0/118 (0.00%) 
Aspergillus infection  1  0/237 (0.00%)  1/118 (0.85%) 
Clostridium difficile colitis  1  1/237 (0.42%)  0/118 (0.00%) 
Enterococcal bacteraemia  1  1/237 (0.42%)  0/118 (0.00%) 
Gastroenteritis  1  1/237 (0.42%)  0/118 (0.00%) 
Klebsiella infection  1  0/237 (0.00%)  1/118 (0.85%) 
Lower respiratory tract infection  1  0/237 (0.00%)  1/118 (0.85%) 
Pneumocystis jirovecii infection  1  0/237 (0.00%)  1/118 (0.85%) 
Pneumonia klebsiella  1  1/237 (0.42%)  0/118 (0.00%) 
Pneumonia necrotising  1  0/237 (0.00%)  1/118 (0.85%) 
Respiratory moniliasis  1  0/237 (0.00%)  1/118 (0.85%) 
Staphylococcal infection  1  1/237 (0.42%)  0/118 (0.00%) 
Streptococcal sepsis  1  1/237 (0.42%)  0/118 (0.00%) 
Injury, poisoning and procedural complications     
Post lumbar puncture syndrome  1  2/237 (0.84%)  1/118 (0.85%) 
Subdural haematoma  1  2/237 (0.84%)  1/118 (0.85%) 
Investigations     
Blood creatinine increased  1  3/237 (1.27%)  0/118 (0.00%) 
Creatinine renal clearance decreased  1  2/237 (0.84%)  0/118 (0.00%) 
Alanine aminotransferase increased  1  0/237 (0.00%)  1/118 (0.85%) 
Aspartate aminotransferase increased  1  0/237 (0.00%)  1/118 (0.85%) 
Lymphocyte count decreased  1  1/237 (0.42%)  0/118 (0.00%) 
White blood cell count decreased  1  1/237 (0.42%)  0/118 (0.00%) 
Metabolism and nutrition disorders     
Hypokalaemia  1  2/237 (0.84%)  0/118 (0.00%) 
Hyperammonaemia  1  1/237 (0.42%)  0/118 (0.00%) 
Hyperglycaemia  1  1/237 (0.42%)  0/118 (0.00%) 
Hyponatraemia  1  1/237 (0.42%)  0/118 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/237 (0.42%)  0/118 (0.00%) 
Joint swelling  1  1/237 (0.42%)  0/118 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Metastases to bone marrow  1  1/237 (0.42%)  0/118 (0.00%) 
Metastases to central nervous system  1  1/237 (0.42%)  0/118 (0.00%) 
Nervous system disorders     
Encephalopathy  1  2/237 (0.84%)  2/118 (1.69%) 
Cerebral ischaemia  1  1/237 (0.42%)  0/118 (0.00%) 
Cerebrovascular accident  1  1/237 (0.42%)  0/118 (0.00%) 
Encephalitis  1  1/237 (0.42%)  0/118 (0.00%) 
Hepatic encephalopathy  1  1/237 (0.42%)  0/118 (0.00%) 
Intracranial venous sinus thrombosis  1  1/237 (0.42%)  0/118 (0.00%) 
Meningism  1  1/237 (0.42%)  0/118 (0.00%) 
Somnolence  1  0/237 (0.00%)  1/118 (0.85%) 
Renal and urinary disorders     
Renal failure  1  4/237 (1.69%)  2/118 (1.69%) 
Renal failure acute  1  3/237 (1.27%)  2/118 (1.69%) 
Nephropathy toxic  1  1/237 (0.42%)  0/118 (0.00%) 
Renal tubular necrosis  1  1/237 (0.42%)  0/118 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  2/237 (0.84%)  0/118 (0.00%) 
Pulmonary haemorrhage  1  2/237 (0.84%)  0/118 (0.00%) 
Respiratory failure  1  1/237 (0.42%)  1/118 (0.85%) 
Bronchial obstruction  1  1/237 (0.42%)  0/118 (0.00%) 
Bronchospasm  1  1/237 (0.42%)  0/118 (0.00%) 
Dyspnoea  1  1/237 (0.42%)  0/118 (0.00%) 
Interstitial lung disease  1  0/237 (0.00%)  1/118 (0.85%) 
Pneumonitis  1  0/237 (0.00%)  1/118 (0.85%) 
Pneumothorax  1  1/237 (0.42%)  0/118 (0.00%) 
Respiratory distress  1  1/237 (0.42%)  0/118 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash papular  1  1/237 (0.42%)  0/118 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  0/237 (0.00%)  1/118 (0.85%) 
Hypotension  1  1/237 (0.42%)  0/118 (0.00%) 
Thrombosis  1  0/237 (0.00%)  1/118 (0.85%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (16.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Liposomal Amphotericin B Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   233/237 (98.31%)   114/118 (96.61%) 
Blood and lymphatic system disorders     
Anaemia  1  49/237 (20.68%)  27/118 (22.88%) 
Febrile neutropenia  1  50/237 (21.10%)  26/118 (22.03%) 
Neutropenia  1  40/237 (16.88%)  26/118 (22.03%) 
Thrombocytopenia  1  42/237 (17.72%)  14/118 (11.86%) 
Coagulopathy  1  13/237 (5.49%)  9/118 (7.63%) 
Cardiac disorders     
Tachycardia  1  13/237 (5.49%)  8/118 (6.78%) 
Ear and labyrinth disorders     
Vertigo  1  14/237 (5.91%)  8/118 (6.78%) 
Gastrointestinal disorders     
Nausea  1  118/237 (49.79%)  50/118 (42.37%) 
Vomiting  1  75/237 (31.65%)  43/118 (36.44%) 
Constipation  1  74/237 (31.22%)  40/118 (33.90%) 
Diarrhoea  1  66/237 (27.85%)  36/118 (30.51%) 
Abdominal pain  1  55/237 (23.21%)  35/118 (29.66%) 
Abdominal pain upper  1  39/237 (16.46%)  14/118 (11.86%) 
Haemorrhoids  1  18/237 (7.59%)  12/118 (10.17%) 
Stomatitis  1  14/237 (5.91%)  11/118 (9.32%) 
Dyspepsia  1  14/237 (5.91%)  4/118 (3.39%) 
General disorders     
Pyrexia  1  65/237 (27.43%)  37/118 (31.36%) 
Mucosal inflammation  1  61/237 (25.74%)  32/118 (27.12%) 
Oedema peripheral  1  56/237 (23.63%)  18/118 (15.25%) 
Asthenia  1  32/237 (13.50%)  19/118 (16.10%) 
Fatigue  1  17/237 (7.17%)  10/118 (8.47%) 
Chest pain  1  18/237 (7.59%)  8/118 (6.78%) 
Chills  1  17/237 (7.17%)  9/118 (7.63%) 
Oedema  1  15/237 (6.33%)  6/118 (5.08%) 
Pain  1  10/237 (4.22%)  11/118 (9.32%) 
Hepatobiliary disorders     
Hyperbilirubinaemia  1  6/237 (2.53%)  7/118 (5.93%) 
Infections and infestations     
Oral herpes  1  22/237 (9.28%)  7/118 (5.93%) 
Oral candidiasis  1  8/237 (3.38%)  11/118 (9.32%) 
Bacterial infection  1  12/237 (5.06%)  6/118 (5.08%) 
Pneumonia  1  15/237 (6.33%)  3/118 (2.54%) 
Folliculitis  1  10/237 (4.22%)  6/118 (5.08%) 
Investigations     
Antithrombin III decreased  1  33/237 (13.92%)  14/118 (11.86%) 
Blood fibrinogen decreased  1  19/237 (8.02%)  8/118 (6.78%) 
Alanine aminotransferase increased  1  17/237 (7.17%)  9/118 (7.63%) 
Aspartate aminotransferase increased  1  19/237 (8.02%)  4/118 (3.39%) 
Blood bilirubin increased  1  16/237 (6.75%)  4/118 (3.39%) 
Blood creatinine increased  1  20/237 (8.44%)  0/118 (0.00%) 
Weight decreased  1  13/237 (5.49%)  4/118 (3.39%) 
Metabolism and nutrition disorders     
Hypokalaemia  1  83/237 (35.02%)  21/118 (17.80%) 
Hyperglycaemia  1  22/237 (9.28%)  11/118 (9.32%) 
Hypoalbuminaemia  1  24/237 (10.13%)  9/118 (7.63%) 
Decreased appetite  1  18/237 (7.59%)  9/118 (7.63%) 
Hypocalcaemia  1  18/237 (7.59%)  7/118 (5.93%) 
Fluid retention  1  15/237 (6.33%)  6/118 (5.08%) 
Hyperuricaemia  1  13/237 (5.49%)  4/118 (3.39%) 
Hypomagnesaemia  1  12/237 (5.06%)  5/118 (4.24%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  34/237 (14.35%)  16/118 (13.56%) 
Neck pain  1  14/237 (5.91%)  9/118 (7.63%) 
Pain in extremity  1  8/237 (3.38%)  10/118 (8.47%) 
Bone pain  1  11/237 (4.64%)  6/118 (5.08%) 
Nervous system disorders     
Headache  1  84/237 (35.44%)  45/118 (38.14%) 
Dizziness  1  11/237 (4.64%)  12/118 (10.17%) 
Paraesthesia  1  14/237 (5.91%)  9/118 (7.63%) 
Psychiatric disorders     
Insomnia  1  32/237 (13.50%)  17/118 (14.41%) 
Anxiety  1  19/237 (8.02%)  15/118 (12.71%) 
Depression  1  12/237 (5.06%)  5/118 (4.24%) 
Agitation  1  5/237 (2.11%)  7/118 (5.93%) 
Reproductive system and breast disorders     
Vaginal haemorrhage  1  2/237 (0.84%)  6/118 (5.08%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  29/237 (12.24%)  17/118 (14.41%) 
Epistaxis  1  20/237 (8.44%)  16/118 (13.56%) 
Dyspnoea  1  19/237 (8.02%)  10/118 (8.47%) 
Oropharyngeal pain  1  15/237 (6.33%)  13/118 (11.02%) 
Skin and subcutaneous tissue disorders     
Rash  1  39/237 (16.46%)  11/118 (9.32%) 
Erythema  1  19/237 (8.02%)  5/118 (4.24%) 
Alopecia  1  17/237 (7.17%)  6/118 (5.08%) 
Pruritus  1  13/237 (5.49%)  4/118 (3.39%) 
Vascular disorders     
Hypotension  1  17/237 (7.17%)  15/118 (12.71%) 
Hypertension  1  12/237 (5.06%)  7/118 (5.93%) 
Haematoma  1  15/237 (6.33%)  3/118 (2.54%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (16.1)
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.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:

  • The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or
  • The study has been completed at all study sites for at least 2 years
Results Point of Contact
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences, Inc.
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01259713     History of Changes
Other Study ID Numbers: GS-EU-131-0247
2010-019562-91 ( EudraCT Number )
First Submitted: December 10, 2010
First Posted: December 14, 2010
Results First Submitted: March 25, 2015
Results First Posted: April 6, 2015
Last Update Posted: May 7, 2015