Rasburicase Versus Allopurinol in Tumor Patients at Risk for Hyperuricemia and Tumor Lysis Syndrome
Sponsor
Sanofi (Industry)
Overall Status
Completed
CT.gov ID
NCT00230178
Collaborator
(none)
280
15
3
44
18.7
0.4
Study Details
Study Description
Brief Summary
This is a randomized, multi-center, open-label, parallel group study with three arms:
-
Rasburicase alone
-
Rasburicase followed by Allopurinol
-
Allopurinol alone
The primary objective is to compare the adequacy of control of plasma uric acid concentration and the safety profile among the three arms.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
After signing the informed consent and having met the inclusion criteria, patients will be randomized to 1 of the 3 arms and treated for a total duration of 5 days. Patients in all arms will receive chemotherapy beginning 4-24 hours after the first dose of rasburicase or allopurinol.
Study Design
Study Type:
Interventional
Actual Enrollment
:
280 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Evaluation of Single Agent Rasburicase for 5 Days Versus Sequential Treatment With Rasburicase From Day 1 Through 3 Followed by Oral Allopurinol From Day 3 Through 5 (Overlap on Day 3) Versus Single Agent Oral Allopurinol for 5 Days in the Management of Plasma Uric Acid in Adult Patients With Leukemia, Lymphoma, and Solid Tumor Malignancies at Risk for Hyperuricemia and Tumor Lysis Syndrome
Study Start Date
:
Apr 1, 2004
Actual Primary Completion Date
:
Dec 1, 2007
Actual Study Completion Date
:
Dec 1, 2007
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm A Rasburicase alone given as a single agent for 5 days |
Drug: Rasburicase (SR29142)
30-min IV infusion
|
| Experimental: Arm B Rasburicase alone given as a single agent from Day 1 through Day 3, followed by oral allopurinol given from Day 3 through Day 5 (Day 3 is an overlap) |
Drug: Rasburicase (SR29142)
30-min IV infusion
Drug: Allopurinol
Oral administration
|
| Active Comparator: Arm C Oral allopurinol alone given as a single agent for 5 days |
Drug: Allopurinol
Oral administration
|
Outcome Measures
Primary Outcome Measures
- Plasma Uric Acid Responder [Day 3 through Day 7]
Number of patients responding to treatment defined as plasma uric acid levels at Day 3 through Day 7 <7.5 mg/dl.
Secondary Outcome Measures
- Plasma Uric Acid [Day 1 to Day 7]
Area under the curve concentration versus time curve extrapolated to infinity (AUC) of plasma uric acid values
- Time to Uric Acid Control [Day 1 to Day 7]
Time from the first dose of study drug to the time at which plasma uric acid concentrations were determined <=7.5 mg/dl, measured -4, 4, 24, 48, 72, 96, 120, and 144 hours after infusion.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
- Meets high risk or at potential risk for tumor lysis syndrome (TLS):
A patient is at high risk for TLS if he/she presents with:
-
Hyperuricemia of malignancy (plasma uric acid > 7.5 mg/dL);
-
A diagnosis of very aggressive lymphoma/leukemia based on the Revised European-American Lymphoma (REAL) classification of lymphoma/leukemia;
-
Acute myeloid leukemia (AML);
-
Chronic myeloid leukemia (CML) in blast crisis; or
-
High grade myelodysplastic syndrome (refractory anemia with excess blast, chronic myelomonocytic leukemia, and refractory anemia with excess blast in transformation) only if they have > 10% bone marrow blast involvement and are given aggressive treatment similar to AML.
A patient is at potential risk for TLS if he/she presents with:
-
A diagnosis of aggressive lymphoma/leukemia based on the REAL classification of lymphoma/leukemia plus 1 or more of the following criteria:
-
Lactate dehydrogenase (LDH) >= 2 x upper limit of normal (ULN) (IU/L)
-
Stage III-IV disease
-
Stage I-II disease with at least 1 lymph node/tumor > 5 cm in diameter
In addition to the above-mentioned eligibility criteria, the patients should have the following criteria:
-
Eastern Cooperative Oncology Group (ECOG) performance status 0-3
-
Age >= 18 years
-
Life expectancy > 3 months
-
Negative pregnancy test (females of child bearing potential) and use of effective contraceptive method (for both males and females). A pregnancy test may be performed on serum or urine human chorionic gonadotropin (HCG).
-
Signed written informed consent
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Alta Bates Comprehensive Cancer Center | Berkeley | California | United States | 94704 |
| 2 | UCLA Medical Center | Los Angeles | California | United States | 90095 |
| 3 | Rocky Mountain Cancer Center | Denver | Colorado | United States | 80218 |
| 4 | University of Florida Health Science Center at Jacksonville | Jacksonville | Florida | United States | 32209 |
| 5 | Ochsner Clinic Foundation | New Orleans | Louisiana | United States | 70121 |
| 6 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 7 | New York Methodist Hospital | Brooklyn | New York | United States | 11215 |
| 8 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
| 9 | University of Rochester Medical Center | Rochester | New York | United States | 14642 |
| 10 | New York Medical College | Valhalla | New York | United States | 10595 |
| 11 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 12 | Oregon Health and Sciences University | Portland | Oregon | United States | 97201 |
| 13 | University of Pennsylvania Health Systems | Philadelphia | Pennsylvania | United States | 19194 |
| 14 | University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 15 | Mary Babb Randolph Cancer Center | Morgantown | West Virginia | United States | 26506-9162 |
Sponsors and Collaborators
- Sanofi
Investigators
- Study Director: International Clinical Development, Sanofi
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00230178
Other Study ID Numbers:
- EFC4978
First Posted:
Sep 30, 2005
Last Update Posted:
Jan 12, 2010
Last Verified:
Jan 1, 2010
Keywords provided by ,
,
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Rasburicase | Rasburicase + Allopurinol | Allopurinol |
|---|---|---|---|
| Arm/Group Description | Rasburicase (0.20 mg/kg/day) given as a single agent for 5 days | Rasburicase (0.20 mg/kg/day) given alone as a single agent from Day 1 through Day 3, followed by oral allopurinol (300 mg/day) given from Day 3 through Day 5 (Day 3 is an overlap) | Allopurinol (300 mg/day) given alone as a single agent for 5 days |
| Period Title: Overall Study | |||
| STARTED | 94 | 93 | 93 |
| Treated | 92 | 92 | 91 |
| COMPLETED | 90 | 86 | 86 |
| NOT COMPLETED | 4 | 7 | 7 |
Baseline Characteristics
| Arm/Group Title | Rasburicase | Rasburicase + Allopurinol | Allopurinol | Total |
|---|---|---|---|---|
| Arm/Group Description | Rasburicase (0.20 mg/kg/day) given as a single agent for 5 days | Rasburicase (0.20 mg/kg/day) given alone as a single agent from Day 1 through Day 3, followed by oral allopurinol (300 mg/day) given from Day 3 through Day 5 (Day 3 is an overlap) | Allopurinol (300 mg/day) given alone as a single agent for 5 days | Total of all reporting groups |
| Overall Participants | 94 | 93 | 93 | 280 |
| Age, Customized (participants) [Number] | ||||
| <65 years |
63
67%
|
65
69.9%
|
69
74.2%
|
197.0
70.4%
|
| >=65 years |
31
33%
|
28
30.1%
|
24
25.8%
|
83.0
29.6%
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
35
37.2%
|
42
45.2%
|
29
31.2%
|
106.0
37.9%
|
| Male |
59
62.8%
|
51
54.8%
|
64
68.8%
|
174.0
62.1%
|
Outcome Measures
| Title | Plasma Uric Acid Responder |
|---|---|
| Description | Number of patients responding to treatment defined as plasma uric acid levels at Day 3 through Day 7 <7.5 mg/dl. |
| Time Frame | Day 3 through Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rasburicase | Rasburicase + Allopurinol | Allopurinol |
|---|---|---|---|
| Arm/Group Description | Rasburicase (0.20 mg/kg/day) given as a single agent for 5 days | Rasburicase (0.20 mg/kg/day) given alone as a single agent from Day 1 through Day 3, followed by oral allopurinol (300 mg/day) given from Day 3 through Day 5 (Day 3 is an overlap) | Allopurinol (300 mg/day) given alone as a single agent for 5 days |
| Measure Participants | 92 | 92 | 91 |
| Responder |
80
85.1%
|
72
77.4%
|
60
64.5%
|
| Non-Responder |
12
12.8%
|
20
21.5%
|
31
33.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rasburicase, Allopurinol |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0009 |
| Comments | ||
| Method | Wilson's method | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in response rate % |
| Estimated Value | 21 | |
| Confidence Interval |
() 95% 8.6 to 32.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Rasburicase + Allopurinol, Allopurinol |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0632 |
| Comments | ||
| Method | Wilson's method | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in response rate % |
| Estimated Value | 12.3 | |
| Confidence Interval |
() 95% -0.9 to 25.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Plasma Uric Acid |
|---|---|
| Description | Area under the curve concentration versus time curve extrapolated to infinity (AUC) of plasma uric acid values |
| Time Frame | Day 1 to Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the modified ITT-population with an evaluation of plasma uric acid AUC. |
| Arm/Group Title | Rasburicase | Rasburicase + Allopurinol | Allopurinol |
|---|---|---|---|
| Arm/Group Description | Rasburicase (0.20 mg/kg/day) given as a single agent for 5 days | Rasburicase (0.20 mg/kg/day) given alone as a single agent from Day 1 through Day 3, followed by oral allopurinol (300 mg/day) given from Day 3 through Day 5 (Day 3 is an overlap) | Allopurinol (300 mg/day) given alone as a single agent for 5 days |
| Measure Participants | 80 | 77 | 72 |
| Mean (Standard Deviation) [mg*h/dL] |
77.25
(57.17)
|
108.05
(70.49)
|
646.22
(285.29)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rasburicase, Allopurinol |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Rasburicase + Allopurinol, Allopurinol |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Title | Time to Uric Acid Control |
|---|---|
| Description | Time from the first dose of study drug to the time at which plasma uric acid concentrations were determined <=7.5 mg/dl, measured -4, 4, 24, 48, 72, 96, 120, and 144 hours after infusion. |
| Time Frame | Day 1 to Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on a subgroup of patients from the mITT-population with hyperuricemia immediately prior to the first dose of study drug. |
| Arm/Group Title | Rasburicase | Rasburicase + Allopurinol | Allopurinol |
|---|---|---|---|
| Arm/Group Description | Rasburicase (0.20 mg/kg/day) given as a single agent for 5 days | Rasburicase (0.20 mg/kg/day) given alone as a single agent from Day 1 through Day 3, followed by oral allopurinol (300 mg/day) given from Day 3 through Day 5 (Day 3 is an overlap) | Allopurinol (300 mg/day) given alone as a single agent for 5 days |
| Measure Participants | 18 | 12 | 16 |
| Median (95% Confidence Interval) [Hours] |
4.1
|
4.1
|
27.0
|
Adverse Events
| Time Frame | Time from the first study drug intake until a maximum follow-up of 30 days after the last dose of antihyperuricemic treatment. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Reported events are treatment emergent adverse events within the time frame mentioned above. | |||||
| Arm/Group Title | Rasburicase | Rasburicase + Allopurinol | Allopurinol | |||
| Arm/Group Description | Rasburicase (0.20 mg/kg/day) given as a single agent for 5 days | Rasburicase (0.20 mg/kg/day) given alone as a single agent from Day 1 through Day 3, followed by oral allopurinol (300 mg/day) given from Day 3 through Day 5 (Day 3 is an overlap) | Allopurinol (300 mg/day) given alone as a single agent for 5 days | |||
All Cause Mortality |
||||||
| Rasburicase | Rasburicase + Allopurinol | Allopurinol | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Rasburicase | Rasburicase + Allopurinol | Allopurinol | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 36/92 (39.1%) | 32/92 (34.8%) | 29/91 (31.9%) | |||
| Blood and lymphatic system disorders | ||||||
| Febrile neutropenia | 4/92 (4.3%) | 3/92 (3.3%) | 5/91 (5.5%) | |||
| Thrombocytopenia | 2/92 (2.2%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Neutropenia | 1/92 (1.1%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Pancytopenia | 1/92 (1.1%) | 0/92 (0%) | 1/91 (1.1%) | |||
| Coagulopathy | 0/92 (0%) | 0/92 (0%) | 1/91 (1.1%) | |||
| Cardiac disorders | ||||||
| Atrial fibrillation | 2/92 (2.2%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Cardio-respiratory arrest | 1/92 (1.1%) | 0/92 (0%) | 1/91 (1.1%) | |||
| Acute myocardial infarction | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Angina pectoris | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Myocardial infarction | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Pericardial effusion | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Tachycardia | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Supraventricular tachycardia | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 2/92 (2.2%) | 0/92 (0%) | 1/91 (1.1%) | |||
| Haemorrhoids | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Proctalgia | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Rectal haemorrhage | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Small intestinal obstruction | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Constipation | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Diarrhoea | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Peritonitis | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Colitis | 0/92 (0%) | 0/92 (0%) | 1/91 (1.1%) | |||
| Gastrointestinal haemorrhage | 0/92 (0%) | 0/92 (0%) | 1/91 (1.1%) | |||
| General disorders | ||||||
| Multi-organ failure | 2/92 (2.2%) | 2/92 (2.2%) | 2/91 (2.2%) | |||
| Pyrexia | 2/92 (2.2%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Adverse drug reaction | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Disease progression | 0/92 (0%) | 1/92 (1.1%) | 1/91 (1.1%) | |||
| Death | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Hepatobiliary disorders | ||||||
| Cholelithiasis | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Hyperbilirubinaemia | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Hepatic failure | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Hepatic steatosis | 0/92 (0%) | 0/92 (0%) | 1/91 (1.1%) | |||
| Immune system disorders | ||||||
| Hypersensitivity | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Drug hypersensitivity | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Infections and infestations | ||||||
| Neutropenic infection | 5/92 (5.4%) | 4/92 (4.3%) | 8/91 (8.8%) | |||
| Neutropenic sepsis | 5/92 (5.4%) | 1/92 (1.1%) | 3/91 (3.3%) | |||
| Sepsis | 1/92 (1.1%) | 1/92 (1.1%) | 1/91 (1.1%) | |||
| Infection | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Lung infection | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Septic shock | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Systemic mycosis | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Clostridium difficile colitis | 0/92 (0%) | 1/92 (1.1%) | 1/91 (1.1%) | |||
| Abdominal abscess | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Appendicitis | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Catheter site infection | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Muscle abscess | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Urinary tract infection | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Lobar pneumonia | 0/92 (0%) | 0/92 (0%) | 1/91 (1.1%) | |||
| Pneumonia | 0/92 (0%) | 0/92 (0%) | 1/91 (1.1%) | |||
| Sinusitis fungal | 0/92 (0%) | 0/92 (0%) | 1/91 (1.1%) | |||
| Injury, poisoning and procedural complications | ||||||
| Drug toxicity | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Subdural haemorrhage | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Accidental overdose | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Renal injury | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Subdural haematoma | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Investigations | ||||||
| Liver function test abnormal | 0/92 (0%) | 1/92 (1.1%) | 1/91 (1.1%) | |||
| Blood pressure increased | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Hypoglycaemia | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Hyperkalaemia | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Hyponatraemia | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Dehydration | 0/92 (0%) | 0/92 (0%) | 1/91 (1.1%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Musculoskeletal chest pain | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Tumor lysis syndrom | 1/92 (1.1%) | 1/92 (1.1%) | 3/91 (3.3%) | |||
| Acute myeloid leukaemia | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Nervous system disorders | ||||||
| Neurotoxicity | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Peripheral motor neuropathy | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Reversible posterior leukoencephalopathy syndrom | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Haemorrhage intracanial | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Headache | 0/92 (0%) | 0/92 (0%) | 1/91 (1.1%) | |||
| Neurological symptom | 0/92 (0%) | 0/92 (0%) | 1/91 (1.1%) | |||
| Psychiatric disorders | ||||||
| Agitation | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Completed suicide | 0/92 (0%) | 0/92 (0%) | 1/91 (1.1%) | |||
| Mania | 0/92 (0%) | 0/92 (0%) | 1/91 (1.1%) | |||
| Renal and urinary disorders | ||||||
| Renal failure acute | 1/92 (1.1%) | 1/92 (1.1%) | 1/91 (1.1%) | |||
| Renal failure | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Respiratory failure | 2/92 (2.2%) | 3/92 (3.3%) | 1/91 (1.1%) | |||
| Respiratory distress | 2/92 (2.2%) | 0/92 (0%) | 0/91 (0%) | |||
| Pulmonary haemorrhage | 1/92 (1.1%) | 3/92 (3.3%) | 0/91 (0%) | |||
| Acute respiratory distress syndrome | 1/92 (1.1%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Pleuritic pain | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Pulmonary embolism | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Pulmonary edema | 1/92 (1.1%) | 0/92 (0%) | 0/91 (0%) | |||
| Epistaxis | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Dyspnoea | 0/92 (0%) | 0/92 (0%) | 1/91 (1.1%) | |||
| Vascular disorders | ||||||
| Hypertension | 0/92 (0%) | 1/92 (1.1%) | 0/91 (0%) | |||
| Deep vein thrombosis | 0/92 (0%) | 0/92 (0%) | 1/91 (1.1%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Rasburicase | Rasburicase + Allopurinol | Allopurinol | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 91/92 (98.9%) | 92/92 (100%) | 90/91 (98.9%) | |||
| Blood and lymphatic system disorders | ||||||
| Thrombocytopenia | 51/92 (55.4%) | 49/92 (53.3%) | 48/91 (52.7%) | |||
| Neutropenia | 49/92 (53.3%) | 44/92 (47.8%) | 45/91 (49.5%) | |||
| Anaemia | 31/92 (33.7%) | 31/92 (33.7%) | 43/91 (47.3%) | |||
| Febrile neutropenia | 19/92 (20.7%) | 22/92 (23.9%) | 21/91 (23.1%) | |||
| Leukopenia | 15/92 (16.3%) | 12/92 (13%) | 11/91 (12.1%) | |||
| Lymphopenia | 1/92 (1.1%) | 5/92 (5.4%) | 1/91 (1.1%) | |||
| Cardiac disorders | ||||||
| Tachycardia | 20/92 (21.7%) | 23/92 (25%) | 22/91 (24.2%) | |||
| Atrial fibrillation | 6/92 (6.5%) | 3/92 (3.3%) | 3/91 (3.3%) | |||
| Angina pectoris | 5/92 (5.4%) | 4/92 (4.3%) | 0/91 (0%) | |||
| Bradycardia | 1/92 (1.1%) | 6/92 (6.5%) | 4/91 (4.4%) | |||
| Ear and labyrinth disorders | ||||||
| Ear and labyrinth disorder | 1/92 (1.1%) | 7/92 (7.6%) | 5/91 (5.5%) | |||
| Eye disorders | ||||||
| Dry eye | 0/92 (0%) | 5/92 (5.4%) | 0/91 (0%) | |||
| Gastrointestinal disorders | ||||||
| Nausea | 53/92 (57.6%) | 56/92 (60.9%) | 50/91 (54.9%) | |||
| Diarrhoea | 52/92 (56.5%) | 52/92 (56.5%) | 51/91 (56%) | |||
| Vomiting | 35/92 (38%) | 34/92 (37%) | 28/91 (30.8%) | |||
| Constipation | 25/92 (27.2%) | 25/92 (27.2%) | 31/91 (34.1%) | |||
| Abdominal pain | 18/92 (19.6%) | 31/92 (33.7%) | 22/91 (24.2%) | |||
| Abdominal pain upper | 10/92 (10.9%) | 6/92 (6.5%) | 16/91 (17.6%) | |||
| Dyspepsia | 9/92 (9.8%) | 7/92 (7.6%) | 12/91 (13.2%) | |||
| Abdominal distension | 8/92 (8.7%) | 8/92 (8.7%) | 12/91 (13.2%) | |||
| Haemorrhoids | 8/92 (8.7%) | 4/92 (4.3%) | 3/91 (3.3%) | |||
| Flatulence | 6/92 (6.5%) | 8/92 (8.7%) | 7/91 (7.7%) | |||
| Proctalgia | 4/92 (4.3%) | 5/92 (5.4%) | 5/91 (5.5%) | |||
| Oral pain | 4/92 (4.3%) | 4/92 (4.3%) | 8/91 (8.8%) | |||
| Stomatitis | 3/92 (3.3%) | 6/92 (6.5%) | 7/91 (7.7%) | |||
| Dysphagia | 3/92 (3.3%) | 6/92 (6.5%) | 1/91 (1.1%) | |||
| Rectal haemorrhage | 3/92 (3.3%) | 3/92 (3.3%) | 5/91 (5.5%) | |||
| Abdominal discomfort | 2/92 (2.2%) | 5/92 (5.4%) | 7/91 (7.7%) | |||
| Dry mouth | 2/92 (2.2%) | 5/92 (5.4%) | 7/91 (7.7%) | |||
| General disorders | ||||||
| Oedema peripheral | 46/92 (50%) | 40/92 (43.5%) | 39/91 (42.9%) | |||
| Pyrexia | 44/92 (47.8%) | 56/92 (60.9%) | 51/91 (56%) | |||
| Chills | 26/92 (28.3%) | 33/92 (35.9%) | 33/91 (36.3%) | |||
| Mucosal inflammation | 23/92 (25%) | 25/92 (27.2%) | 24/91 (26.4%) | |||
| Fatigue | 19/92 (20.7%) | 28/92 (30.4%) | 34/91 (37.4%) | |||
| Asthenia | 12/92 (13%) | 12/92 (13%) | 19/91 (20.9%) | |||
| Catheter site pain | 9/92 (9.8%) | 4/92 (4.3%) | 8/91 (8.8%) | |||
| Pain | 8/92 (8.7%) | 10/92 (10.9%) | 7/91 (7.7%) | |||
| Oedema | 6/92 (6.5%) | 2/92 (2.2%) | 6/91 (6.6%) | |||
| Catheter site related reaction | 5/92 (5.4%) | 2/92 (2.2%) | 4/91 (4.4%) | |||
| Catheter site erythema | 5/92 (5.4%) | 1/92 (1.1%) | 8/91 (8.8%) | |||
| Catheter site haemorrhage | 4/92 (4.3%) | 1/92 (1.1%) | 9/91 (9.9%) | |||
| Malaise | 3/92 (3.3%) | 2/92 (2.2%) | 5/91 (5.5%) | |||
| Hepatobiliary disorders | ||||||
| Hyperbilirubinaemia | 14/92 (15.2%) | 13/92 (14.1%) | 7/91 (7.7%) | |||
| Infections and infestations | ||||||
| Sepsis | 10/92 (10.9%) | 6/92 (6.5%) | 3/91 (3.3%) | |||
| Bacteraemia | 9/92 (9.8%) | 7/92 (7.6%) | 16/91 (17.6%) | |||
| Pneumonia | 9/92 (9.8%) | 2/92 (2.2%) | 7/91 (7.7%) | |||
| Cellulitis | 6/92 (6.5%) | 0/92 (0%) | 4/91 (4.4%) | |||
| Oral candidiasis | 5/92 (5.4%) | 1/92 (1.1%) | 1/91 (1.1%) | |||
| Injury, poisoning and procedural complications | ||||||
| Contusion | 6/92 (6.5%) | 7/92 (7.6%) | 5/91 (5.5%) | |||
| Procedural pain | 5/92 (5.4%) | 5/92 (5.4%) | 2/91 (2.2%) | |||
| Transfusion reaction | 4/92 (4.3%) | 7/92 (7.6%) | 8/91 (8.8%) | |||
| Investigations | ||||||
| Aspartate aminotransferase increased | 15/92 (16.3%) | 22/92 (23.9%) | 20/91 (22%) | |||
| Blood bilirubin increased | 14/92 (15.2%) | 11/92 (12%) | 13/91 (14.3%) | |||
| Alanine aminotransferase increased | 10/92 (10.9%) | 25/92 (27.2%) | 16/91 (17.6%) | |||
| Blood creatinine increased | 7/92 (7.6%) | 8/92 (8.7%) | 9/91 (9.9%) | |||
| Blood alkaline phophatase increased | 6/92 (6.5%) | 5/92 (5.4%) | 4/91 (4.4%) | |||
| Blood pressure increased | 4/92 (4.3%) | 5/92 (5.4%) | 1/91 (1.1%) | |||
| Platelet count decreased | 4/92 (4.3%) | 5/92 (5.4%) | 6/91 (6.6%) | |||
| Blood lactate dehydrogenase decreased | 2/92 (2.2%) | 7/92 (7.6%) | 3/91 (3.3%) | |||
| Weight decreased | 2/92 (2.2%) | 6/92 (6.5%) | 5/91 (5.5%) | |||
| Haemoglobin decreased | 2/92 (2.2%) | 5/92 (5.4%) | 6/91 (6.6%) | |||
| Blood alkaline phosphatase decreased | 1/92 (1.1%) | 5/92 (5.4%) | 3/91 (3.3%) | |||
| White blood cell count decreased | 1/92 (1.1%) | 5/92 (5.4%) | 3/91 (3.3%) | |||
| Blood phosphorus increased | 1/92 (1.1%) | 2/92 (2.2%) | 7/91 (7.7%) | |||
| Metabolism and nutrition disorders | ||||||
| Hypokalaemia | 35/92 (38%) | 32/92 (34.8%) | 36/91 (39.6%) | |||
| Hypocalcaemia | 31/92 (33.7%) | 41/92 (44.6%) | 44/91 (48.4%) | |||
| Hyperglycaemia | 27/92 (29.3%) | 34/92 (37%) | 35/91 (38.5%) | |||
| Hypoalbuminaemia | 25/92 (27.2%) | 24/92 (26.1%) | 27/91 (29.7%) | |||
| Hyponatraemia | 25/92 (27.2%) | 21/92 (22.8%) | 23/91 (25.3%) | |||
| Anorexia | 20/92 (21.7%) | 23/92 (25%) | 25/91 (27.5%) | |||
| Hypophosphataemia | 16/92 (17.4%) | 21/92 (22.8%) | 15/91 (16.5%) | |||
| Hypomagnesaemia | 14/92 (15.2%) | 15/92 (16.3%) | 14/91 (15.4%) | |||
| Fluid overload | 11/92 (12%) | 6/92 (6.5%) | 3/91 (3.3%) | |||
| Hyperphosphataemia | 9/92 (9.8%) | 14/92 (15.2%) | 8/91 (8.8%) | |||
| Hyperkalaemia | 7/92 (7.6%) | 4/92 (4.3%) | 4/91 (4.4%) | |||
| Decreased appetite | 5/92 (5.4%) | 4/92 (4.3%) | 6/91 (6.6%) | |||
| Hypernatraemia | 5/92 (5.4%) | 3/92 (3.3%) | 3/91 (3.3%) | |||
| Hyperphosphatasaemia | 2/92 (2.2%) | 7/92 (7.6%) | 6/91 (6.6%) | |||
| Hypoglycaemia | 1/92 (1.1%) | 6/92 (6.5%) | 4/91 (4.4%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 12/92 (13%) | 12/92 (13%) | 15/91 (16.5%) | |||
| Arthralgia | 10/92 (10.9%) | 11/92 (12%) | 9/91 (9.9%) | |||
| Musculoskeletal chest pain | 8/92 (8.7%) | 7/92 (7.6%) | 11/91 (12.1%) | |||
| Pain in extremity | 7/92 (7.6%) | 12/92 (13%) | 18/91 (19.8%) | |||
| Musculoskeletal pain | 3/92 (3.3%) | 8/92 (8.7%) | 6/91 (6.6%) | |||
| Myalgia | 2/92 (2.2%) | 7/92 (7.6%) | 3/91 (3.3%) | |||
| Neck pain | 1/92 (1.1%) | 3/92 (3.3%) | 5/91 (5.5%) | |||
| Nervous system disorders | ||||||
| Headache | 25/92 (27.2%) | 31/92 (33.7%) | 33/91 (36.3%) | |||
| Dizziness | 14/92 (15.2%) | 17/92 (18.5%) | 19/91 (20.9%) | |||
| Lethargy | 8/92 (8.7%) | 6/92 (6.5%) | 3/91 (3.3%) | |||
| Dysgeusia | 6/92 (6.5%) | 6/92 (6.5%) | 6/91 (6.6%) | |||
| Somnolence | 5/92 (5.4%) | 2/92 (2.2%) | 4/91 (4.4%) | |||
| Syncope | 2/92 (2.2%) | 2/92 (2.2%) | 6/91 (6.6%) | |||
| Paraesthesia | 2/92 (2.2%) | 2/92 (2.2%) | 5/91 (5.5%) | |||
| Sinus headache | 0/92 (0%) | 5/92 (5.4%) | 1/91 (1.1%) | |||
| Psychiatric disorders | ||||||
| Anxiety | 22/92 (23.9%) | 16/92 (17.4%) | 16/91 (17.6%) | |||
| Insomnia | 17/92 (18.5%) | 27/92 (29.3%) | 34/91 (37.4%) | |||
| Confusional state | 15/92 (16.3%) | 12/92 (13%) | 11/91 (12.1%) | |||
| Depression | 12/92 (13%) | 6/92 (6.5%) | 13/91 (14.3%) | |||
| Agitation | 8/92 (8.7%) | 1/92 (1.1%) | 4/91 (4.4%) | |||
| Hallucination | 3/92 (3.3%) | 3/92 (3.3%) | 6/91 (6.6%) | |||
| Renal and urinary disorders | ||||||
| Haematuria | 11/92 (12%) | 11/92 (12%) | 13/91 (14.3%) | |||
| Dysuria | 8/92 (8.7%) | 3/92 (3.3%) | 4/91 (4.4%) | |||
| Proteinuria | 6/92 (6.5%) | 7/92 (7.6%) | 8/91 (8.8%) | |||
| Reproductive system and breast disorders | ||||||
| Reproductive system and breast disorders | 10/92 (10.9%) | 6/92 (6.5%) | 11/91 (12.1%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 20/92 (21.7%) | 18/92 (19.6%) | 17/91 (18.7%) | |||
| Cough | 17/92 (18.5%) | 15/92 (16.3%) | 18/91 (19.8%) | |||
| Epistaxis | 16/92 (17.4%) | 14/92 (15.2%) | 20/91 (22%) | |||
| Pharyngolaryngeal pain | 13/92 (14.1%) | 19/92 (20.7%) | 9/91 (9.9%) | |||
| Hypoxia | 10/92 (10.9%) | 8/92 (8.7%) | 8/91 (8.8%) | |||
| Pleural effusion | 10/92 (10.9%) | 6/92 (6.5%) | 8/91 (8.8%) | |||
| Wheezing | 9/92 (9.8%) | 8/92 (8.7%) | 8/91 (8.8%) | |||
| Rales | 7/92 (7.6%) | 6/92 (6.5%) | 9/91 (9.9%) | |||
| Pleuritic pain | 6/92 (6.5%) | 5/92 (5.4%) | 5/91 (5.5%) | |||
| Pulmonary oedema | 5/92 (5.4%) | 7/92 (7.6%) | 3/91 (3.3%) | |||
| Hiccups | 3/92 (3.3%) | 5/92 (5.4%) | 2/91 (2.2%) | |||
| Dyspnoea exertional | 2/92 (2.2%) | 2/92 (2.2%) | 5/91 (5.5%) | |||
| Rhinorrhoea | 1/92 (1.1%) | 1/92 (1.1%) | 5/91 (5.5%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Rash | 26/92 (28.3%) | 31/92 (33.7%) | 30/91 (33%) | |||
| Petechiae | 16/92 (17.4%) | 13/92 (14.1%) | 12/91 (13.2%) | |||
| Pruritus | 10/92 (10.9%) | 10/92 (10.9%) | 9/91 (9.9%) | |||
| Alopecia | 8/92 (8.7%) | 7/92 (7.6%) | 11/91 (12.1%) | |||
| Erythema | 7/92 (7.6%) | 8/92 (8.7%) | 8/91 (8.8%) | |||
| Hyperhidrosis | 7/92 (7.6%) | 3/92 (3.3%) | 9/91 (9.9%) | |||
| Ecchymosis | 5/92 (5.4%) | 6/92 (6.5%) | 5/91 (5.5%) | |||
| Rash generalised | 4/92 (4.3%) | 4/92 (4.3%) | 5/91 (5.5%) | |||
| Vascular disorders | ||||||
| Hypotension | 27/92 (29.3%) | 24/92 (26.1%) | 23/91 (25.3%) | |||
| Hypertension | 11/92 (12%) | 9/92 (9.8%) | 9/91 (9.9%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
| Name/Title | International Clinical Development, Clinical Study Director |
|---|---|
| Organization | Sanofi-aventis |
| Phone | |
| GV-Contact-us@sanofi-aventis.com |
Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00230178
Other Study ID Numbers:
- EFC4978
First Posted:
Sep 30, 2005
Last Update Posted:
Jan 12, 2010
Last Verified:
Jan 1, 2010