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A Multicenter Clinical Trial of Allopurinol to Prevent Kidney Function Loss in Type 1 Diabetes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02017171
Recruitment Status : Completed
First Posted : December 20, 2013
Results First Posted : November 20, 2020
Last Update Posted : December 4, 2020
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Juvenile Diabetes Research Foundation
Joslin Diabetes Center
University of Minnesota
University of Colorado, Denver
University of Michigan
University of Toronto
Feinberg School of Medicine, Northwestern University
Albert Einstein College of Medicine
Steno Diabetes Center Copenhagen
Washington University School of Medicine
University of Washington
Emory University
University of Calgary
University of Alberta
University of Texas Southwestern Medical Center
BCDiabetes.Ca
Information provided by (Responsible Party):
Alessandro Doria, Joslin Diabetes Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Prevention
Conditions Diabetic Nephropathies
Coronary Artery Disease
Interventions Drug: Allopurinol
Drug: Placebo
Enrollment 530
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Allopurinol Placebo
Hide Arm/Group Description Oral allopurinol at a dose of 100 mg per day for 4 weeks and then at a dose ranging from 200 to 400 mg per day depending on kidney function Oral placebo tablets (Inactive oral tablets identical in appearance to allopurinol tablets)
Period Title: Overall Study
Started 267 263
Completed 205 217
Not Completed 62 46
Reason Not Completed
Death             10             4
Withdrawal by Subject             23             17
Lost to Follow-up             21             20
ESKD             6             2
Miscellaneous             2             3
Arm/Group Title Allopurinol Placebo Total
Hide Arm/Group Description Oral allopurinol at a dose of 100 mg per day for 4 weeks and then at a dose ranging from 200 to 400 mg per day depending on kidney function Oral placebo tablets (Inactive oral tablets identical in appearance to allopurinol tablets) Total of all reporting groups
Overall Number of Baseline Participants 267 263 530
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 267 participants 263 participants 530 participants
50.4  (11.2) 51.8  (10.6) 51.1  (10.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 267 participants 263 participants 530 participants
Female
84
  31.5%
95
  36.1%
179
  33.8%
Male
183
  68.5%
168
  63.9%
351
  66.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 267 participants 263 participants 530 participants
Hispanic or Latino
16
   6.0%
7
   2.7%
23
   4.3%
Not Hispanic or Latino
250
  93.6%
254
  96.6%
504
  95.1%
Unknown or Not Reported
1
   0.4%
2
   0.8%
3
   0.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 267 participants 263 participants 530 participants
American Indian or Alaska Native
1
   0.4%
1
   0.4%
2
   0.4%
Asian
1
   0.4%
5
   1.9%
6
   1.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.4%
1
   0.2%
Black or African American
28
  10.5%
30
  11.4%
58
  10.9%
White
230
  86.1%
216
  82.1%
446
  84.2%
More than one race
5
   1.9%
6
   2.3%
11
   2.1%
Unknown or Not Reported
2
   0.7%
4
   1.5%
6
   1.1%
Body Mass Index   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 265 participants 260 participants 525 participants
29.5  (6.1) 29.5  (5.9) 29.5  (6.0)
[1]
Measure Analysis Population Description: BMI values were missing for two participants in the allopurinol group and three participants in the placebo group.
Glycated hemoglobin (HbA1c)   [1] 
Mean (Standard Deviation)
Unit of measure:  Percent
Number Analyzed 265 participants 263 participants 528 participants
8.2  (1.3) 8.2  (1.3) 8.2  (1.3)
[1]
Measure Analysis Population Description: HbA1c values were missing for two participants in the Allopurinol group
Serum uric acid  
Mean (Standard Deviation)
Unit of measure:  Mg/dl
Number Analyzed 267 participants 263 participants 530 participants
6.1  (1.5) 6.1  (1.5) 6.1  (1.5)
Estimated glomerular filtration rate (eGFR)   [1] 
Mean (Standard Deviation)
Unit of measure:  Ml/min/1.73 m^2
Number Analyzed 267 participants 263 participants 530 participants
75.4  (18.7) 74.0  (19.4) 74.7  (19.1)
[1]
Measure Description: Glomerular filtration rate estimated from serum creatinine with the CKD-EPI equation
Measured (iohexol-based) glomerular filtration rate (iGFR)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Ml/min/1.73 m^2
Number Analyzed 267 participants 262 participants 529 participants
68.7  (17.1) 67.3  (16.7) 68  (16.9)
[1]
Measure Description: Glomerular filtration rate measured by the plasma disappearance of an i.v. bolus of the contrast medium iohexol
[2]
Measure Analysis Population Description: Measured GFR value was missing for one participant in the placebo group
Diabetes duration  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 267 participants 263 participants 530 participants
33.8  (12.2) 35.3  (12.5) 34.6  (12.3)
Systolic blood pressure (mmHg)  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 267 participants 263 participants 530 participants
125.6  (14.7) 126.3  (13.6) 126.0  (14.2)
Diastolic blood pressure (mmHg)  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 267 participants 263 participants 530 participants
71.2  (10.4) 71.3  (10.0) 71.2  (10.2)
Urinary albumin excretion rate (AER)   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Ug/min
Number Analyzed 267 participants 261 participants 528 participants
41.1
(7.7 to 216.0)
43.0
(9.0 to 198.0)
41.6
(8.5 to 207.5)
[1]
Measure Analysis Population Description: Urinary AER values were missing for two participants in the placebo group.
Albuminuria   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 267 participants 261 participants 528 participants
Normoalbuminuria
97
  36.3%
92
  35.2%
189
  35.8%
Microalabuminuria
97
  36.3%
106
  40.6%
203
  38.4%
Macroalbuminuria
73
  27.3%
63
  24.1%
136
  25.8%
[1]
Measure Description: Based on overnight urinary albumin excretion rate (AER): normoalbuminuria: AER<20 ug/min, microalbuminuria: AER 20-199 ug/min, macroalbuminuria: AER => 200 ug/min
[2]
Measure Analysis Population Description: Urinary AER values were missing for two participants in the placebo group.
Use of renin-angiotensin inhibitors  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 267 participants 263 participants 530 participants
247
  92.5%
230
  87.5%
477
  90.0%
Smoking  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 267 participants 263 participants 530 participants
Current
27
  10.1%
31
  11.8%
58
  10.9%
Past
70
  26.2%
80
  30.4%
150
  28.3%
Never
170
  63.7%
152
  57.8%
322
  60.8%
1.Primary Outcome
Title iGFR at the End of the Wash-out Period
Hide Description Glomerular filtration rate (GFR) at the end of the 2-month wash-out period following the 3-year treatment period, measured by the plasma disappearance of non-radioactive iohexol (iGFR) and adjusted for the iGFR at baseline.
Time Frame End of the 2-month wash-out period following the 3-year treatment period (week 164)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat population with missing values being imputed
Arm/Group Title Allopurinol Placebo
Hide Arm/Group Description:
Oral allopurinol at a dose of 100 mg per day for 4 weeks and then at a dose ranging from 200 to 400 mg per day depending on kidney function
Oral placebo tablets (inactive oral tablets identical in appearance to allopurinol tablets).
Overall Number of Participants Analyzed 267 263
Least Squares Mean (95% Confidence Interval)
Unit of Measure: ml/min/1.73 m^2
61.2
(58.1 to 64.2)
61.2
(58.1 to 64.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Allopurinol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.999
Comments p value is not adjusted for multiple comparisons, a priori threshold for statistical significance: p<0.05
Method linear model for correlated errors
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.001
Confidence Interval (2-Sided) 95%
-1.9 to 1.9
Estimation Comments Treatment difference = Allopurinol-Placebo
2.Secondary Outcome
Title eGFR at 4 Months of Treatment
Hide Description Glomerular filtration rate (GFR) at 4 months after randomization, estimated from serum creatinine and cystatin C and adjusted for the eGFR at baseline.
Time Frame 4 months after randomization (week 16)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat population, with missing values being imputed
Arm/Group Title Allopurinol Placebo
Hide Arm/Group Description:
Oral allopurinol at a dose of 100 mg per day for 4 weeks and then at a dose ranging from 200 to 400 mg per day depending on kidney function
Oral placebo tablets (Inactive oral tablets identical in appearance to allopurinol tablets)
Overall Number of Participants Analyzed 267 263
Least Squares Mean (95% Confidence Interval)
Unit of Measure: ml/min/1.73 m2
70.3
(67.3 to 73.3)
70.0
(67.1 to 72.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Allopurinol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-1.6 to 2.2
Estimation Comments Treatment difference = Allopurinol - Placebo
3.Secondary Outcome
Title iGFR the End of Treatment Period
Hide Description Glomerular filtration rate (GFR) at the end of the 3-year treatment period, measured by the plasma disappearance of non-radioactive iohexol (iGFR) and adjusted for the iGFR at baseline.
Time Frame End of the 3-yr treatment period (week 156)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat population, with missing values being imputed
Arm/Group Title Allopurinol Placebo
Hide Arm/Group Description:
Oral allopurinol at a dose of 100 mg per day for 4 weeks and then at a dose ranging from 200 to 400 mg per day depending on kidney function
Oral placebo tablets (Inactive oral tablets identical in appearance to allopurinol tablets)
Overall Number of Participants Analyzed 267 263
Least Squares Mean (95% Confidence Interval)
Unit of Measure: ml/min/1.73 m2
61.3
(58.3 to 64.3)
61.0
(57.9 to 64.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Allopurinol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-1.7 to 2.3
Estimation Comments Treatment difference = Allopurinol - Placebo
4.Secondary Outcome
Title iGFR Time Trajectory
Hide Description Glomerular filtration rate time trajectory estimated from iohexol disappearance GFR (iGFR) measurements at weeks 0, 80, 156, and 164. iGFR slopes were estimated by a linear mixed-effects model for longitudinal iGFR measures using a multiple imputation technique for missing values. Positive values denote increasing GFR over time, negative values denote declining iGFR over time.
Time Frame Weeks 0, 80, 156, and 164 (from baseline to the end of washout period)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat population, with missing values being imputed
Arm/Group Title Allopurinol Placebo
Hide Arm/Group Description:
Oral allopurinol at a dose of 100 mg per day for 4 weeks and then at a dose ranging from 200 to 400 mg per day depending on kidney function
Oral placebo tablets (Inactive oral tablets identical in appearance to allopurinol tablets)
Overall Number of Participants Analyzed 267 263
Least Squares Mean (95% Confidence Interval)
Unit of Measure: ml/min/1.73 m2/year
-3.0
(-3.7 to -2.3)
-2.5
(-3.1 to -1.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Allopurinol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.5 to 0.4
Estimation Comments Treatment difference = Allopurinol - Placebo. Confidence intervals are not adjusted for multiplicity and should not be used to infer treatment effects.
5.Secondary Outcome
Title eGFR Time Trajectory
Hide Description Glomerular filtration rate time trajectory from baseline to end of the 2-month wash-out period (week 164) estimated from quarterly serum creatinine measurements (eGFR). eGFR slopes were estimated by a linear mixed-effects model for longitudinal eGFR measures using a multiple imputation technique for missing values. Positive values denote increasing eGFR over time, negative values denote declining eGFR over time.
Time Frame Weeks 0, 4, 16, 32, 48, 64, 80, 96, 112, 128, 156, and 164 (from baseline to the end of washout period)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat population, with missing values being imputed
Arm/Group Title Allopurinol Placebo
Hide Arm/Group Description:
Oral allopurinol at a dose of 100 mg per day for 4 weeks and then at a dose ranging from 200 to 400 mg per day depending on kidney function
Oral placebo tablets (Inactive oral tablets identical in appearance to allopurinol tablets)
Overall Number of Participants Analyzed 267 263
Least Squares Mean (95% Confidence Interval)
Unit of Measure: ml/min/1.73 m2/year
-2.4
(-2.9 to -1.8)
-2.1
(-2.6 to -1.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Allopurinol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-1.0 to 0.5
Estimation Comments Treatment difference = Allopurinol - Placebo. Confidence intervals are not adjusted for multiplicity and should not be used to infer treatment effects.
6.Secondary Outcome
Title Serum Creatinine Doubling or End Stage Renal Disease (ESRD)
Hide Description Risk of serum creatinine doubling or end stage renal disease (ESRD) in the allopurinol arm as compared to placebo. Results are expressed as the number of participants who experienced an event in each treatment group. The risk of an event in the allopurinol group as compared to the risk in the placebo group is expressed as hazard ratio (estimated by means of proportional hazard regression).
Time Frame Up to the end of the 2-month wash-out period following the 3-year treatment period (Week 0 to Week 164)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Allopurinol Placebo
Hide Arm/Group Description:
Oral allopurinol at a dose of 100 mg per day for 4 weeks and then at a dose ranging from 200 to 400 mg per day depending on kidney function
Oral placebo tablets (Inactive oral tablets identical in appearance to allopurinol tablets)
Overall Number of Participants Analyzed 267 263
Measure Type: Count of Participants
Unit of Measure: Participants
13
   4.9%
11
   4.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Allopurinol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
0.5 to 2.9
Estimation Comments Hazard ratio = Allopurinol / Placebo. Confidence intervals are not adjusted for multiplicity and should not be used to infer treatment effects.
7.Secondary Outcome
Title AER at the End of the Wash-out Period
Hide Description Geometric mean of two urinary albumin excretion (AER) measurements at the end of the 2-month wash-out period following the 3-year treatment period, adjusted for the mean urinary AER at baseline. Results are expressed as least square means of the geometric means in each subject in each group.
Time Frame End of the 2-month wash-out period following the 3-year treatment period (week 164)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat population, with missing values being imputed
Arm/Group Title Allopurinol Placebo
Hide Arm/Group Description:
Oral allopurinol at a dose of 100 mg per day for 4 weeks and then at a dose ranging from 200 to 400 mg per day depending on kidney function
Oral placebo tablets (Inactive oral tablets identical in appearance to allopurinol tablets)
Overall Number of Participants Analyzed 267 263
Least Squares Mean (95% Confidence Interval)
Unit of Measure: ug/min
42.9
(24.7 to 74.4)
31.7
(19.5 to 51.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Allopurinol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio (Final Values)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
1.0 to 1.8
Estimation Comments Ratio = Allopurinol / Placebo. Confidence intervals are not adjusted for multiplicity and should not be used to infer treatment effects.
8.Secondary Outcome
Title AER at the End of the Treatment Period
Hide Description Geometric mean of urinary albumin excretion rate (AER) during the last three months of the treatment period (Visits 15 and 16), adjusted for the mean urinary AER at baseline. Results are expressed as least square means of the geometric means in each subject in each group.
Time Frame Last three months of treatment period (Weeks 142 and 156)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat population, with missing values being imputed
Arm/Group Title Allopurinol Placebo
Hide Arm/Group Description:
Oral allopurinol at a dose of 100 mg per day for 4 weeks and then at a dose ranging from 200 to 400 mg per day depending on kidney function
Oral placebo tablets (Inactive oral tablets identical in appearance to allopurinol tablets)
Overall Number of Participants Analyzed 267 263
Least Squares Mean (95% Confidence Interval)
Unit of Measure: ug/min
47.9
(32.5 to 70.6)
37.4
(25.3 to 55.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Allopurinol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio (Final Values)
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
1.0 to 1.6
Estimation Comments [Not Specified]
Other Statistical Analysis Ratio = Allopurinol / Placebo. Confidence intervals are not adjusted for multiplicity and should not be used to infer treatment effects.
9.Secondary Outcome
Title Fatal or Non-fatal Cardiovascular Events
Hide Description Risk of cardiovascular events defined as the composite of CVD death (ICD-10 code I10 to I74.9), myocardial infarction, stroke (ischemic or hemorrhagic), coronary artery bypass grafting, or percutaneous coronary intervention in the allopurinol arm as compared to placebo.Results are expressed as the number of participants who experienced an event in each treatment group. The risk of an event in the allopurinol group as compared to the risk in the placebo group is expressed as hazard ratio (estimated by means of proportional hazard regression).
Time Frame Up to the end of the 2-month wash-out period following the 3-year treatment period (week 0 to 164)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat population
Arm/Group Title Allopurinol Placebo
Hide Arm/Group Description:
Oral allopurinol at a dose of 100 mg per day for 4 weeks and then at a dose ranging from 200 to 400 mg per day depending on kidney function
Oral placebo tablets (Inactive oral tablets identical in appearance to allopurinol tablets)
Overall Number of Participants Analyzed 267 263
Measure Type: Count of Participants
Unit of Measure: Participants
15
   5.6%
9
   3.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Allopurinol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.9
Confidence Interval (2-Sided) 95%
0.8 to 4.5
Estimation Comments Hazard Ratio = Allopurinol / Placebo. Confidence intervals are not adjusted for multiplicity and should not be used to infer treatment effects.
Time Frame In each participants, adverse event data were collected from randomization to two months after the end of pharmacological treatment, or until study discontinuation for participants who did not complete the study. This corresponds to up to 164 weeks for participants who completed the study.
Adverse Event Reporting Description The definition of Adverse Events and/or Serious Adverse Events correspond to that from the clinicaltrials.gov definitions
 
Arm/Group Title Allopurinol Placebo
Hide Arm/Group Description Oral allopurinol at a dose of 100 mg per day for 4 weeks and then at a dose ranging from 200 to 400 mg per day depending on kidney function Oral placebo tablets (Inactive oral tablets identical in appearance to allopurinol tablets)
All-Cause Mortality
Allopurinol Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   10/267 (3.75%)      4/263 (1.52%)    
Hide Serious Adverse Events
Allopurinol Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   93/267 (34.83%)      82/263 (31.18%)    
Blood and lymphatic system disorders     
Anaemia  1  1/267 (0.37%)  1 1/263 (0.38%)  1
Cardiac disorders     
Acute coronary syndrome  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Acute myocardial infarction  1  7/267 (2.62%)  7 5/263 (1.90%)  6
Angina unstable  1  2/267 (0.75%)  2 1/263 (0.38%)  1
Aortic valve stenosis  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Atrial fibrillation  1  1/267 (0.37%)  1 1/263 (0.38%)  1
Atrial flutter  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Atrioventricular block complete  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Brugada syndrome  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Cardiac arrest  1  2/267 (0.75%)  2 1/263 (0.38%)  1
Cardiac failure  1  1/267 (0.37%)  1 2/263 (0.76%)  2
Cardiac failure congestive  1  3/267 (1.12%)  3 3/263 (1.14%)  4
Coronary artery disease  1  4/267 (1.50%)  4 4/263 (1.52%)  4
Coronary artery stenosis  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Myocardial infarction  1  3/267 (1.12%)  3 2/263 (0.76%)  2
Myocardial ischaemia  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Myocarditis  1  1/267 (0.37%)  2 0/263 (0.00%)  0
Pericarditis  1  1/267 (0.37%)  2 0/263 (0.00%)  0
Endocrine disorders     
Hypercalcaemia of malignancy  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Colonic pseudo-obstruction  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Constipation  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Diabetic gastroparesis  1  2/267 (0.75%)  2 1/263 (0.38%)  2
Diabetic gastropathy  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Diarrhoea  1  2/267 (0.75%)  2 0/263 (0.00%)  0
Gastritis  1  0/267 (0.00%)  0 2/263 (0.76%)  2
Gastrointestinal haemorrhage  1  3/267 (1.12%)  3 0/263 (0.00%)  0
Gastrooesophageal reflux disease  1  1/267 (0.37%)  1 1/263 (0.38%)  1
Impaired gastric emptying  1  2/267 (0.75%)  2 3/263 (1.14%)  5
Oesophageal perforation  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Pancreatitis acute  1  3/267 (1.12%)  3 0/263 (0.00%)  0
Small intestinal obstruction  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Vomiting  1  0/267 (0.00%)  0 1/263 (0.38%)  2
General disorders     
Chest discomfort  1  1/267 (0.37%)  2 1/263 (0.38%)  1
Chest pain  1  4/267 (1.50%)  5 2/263 (0.76%)  2
Death  1  2/267 (0.75%)  2 1/263 (0.38%)  1
Oedema due to renal disease  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Pain  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Sudden cardiac death  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Ulcer  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Hepatobiliary disorders     
Bile duct obstruction  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Infections and infestations     
Appendicitis  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Bursitis infective  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Cellulitis  1  3/267 (1.12%)  3 5/263 (1.90%)  5
Clostridium difficile colitis  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Cystitis escherichia  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Diabetic foot infection  1  0/267 (0.00%)  0 3/263 (1.14%)  3
Extradural abscess  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Gastroenteritis  1  1/267 (0.37%)  1 3/263 (1.14%)  3
Gastroenteritis viral  1  1/267 (0.37%)  1 1/263 (0.38%)  1
Herpes simplex meningitis  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Infected skin ulcer  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Infection  1  0/267 (0.00%)  0 4/263 (1.52%)  4
Lobar pneumonia  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Localised infection  1  1/267 (0.37%)  1 1/263 (0.38%)  1
Osteomyelitis  1  6/267 (2.25%)  8 4/263 (1.52%)  6
Osteomyelitis acute  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Pneumonia  1  4/267 (1.50%)  4 5/263 (1.90%)  5
Pneumonia viral  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Renal abscess  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Sepsis  1  1/267 (0.37%)  1 1/263 (0.38%)  1
Staphylococcal infection  1  2/267 (0.75%)  2 0/263 (0.00%)  0
Upper respiratory tract infection  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Urosepsis  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Injury, poisoning and procedural complications     
Concussion  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Extradural haematoma  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Fall  1  1/267 (0.37%)  1 1/263 (0.38%)  1
Femur fracture  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Fracture  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Fractured sacrum  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Hip fracture  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Humerus fracture  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Multiple injuries  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Patella fracture  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Pelvic fracture  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Road traffic accident  1  2/267 (0.75%)  2 0/263 (0.00%)  0
Spinal compression fracture  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Spinal fracture  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Subdural haematoma  1  0/267 (0.00%)  0 2/263 (0.76%)  2
Transplant dysfunction  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Investigations     
Blood glucose fluctuation  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Laboratory test abnormal  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Metabolism and nutrition disorders     
Dehydration  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Diabetic ketoacidosis  1  15/267 (5.62%)  18 13/263 (4.94%)  17
Fluid overload  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Gout  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Hyperglycaemia  1  3/267 (1.12%)  3 5/263 (1.90%)  5
Hyperglycaemic hyperosmolar nonketotic syndrome  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Hypoglycaemia  1  2/267 (0.75%)  2 9/263 (3.42%)  10
Ketoacidosis  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Intervertebral disc protrusion  1  1/267 (0.37%)  1 1/263 (0.38%)  1
Musculoskeletal pain  1  0/267 (0.00%)  0 2/263 (0.76%)  2
Osteoarthritis  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Rotator cuff syndrome  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Spinal column stenosis  1  0/267 (0.00%)  0 2/263 (0.76%)  2
Arthritis  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast cancer  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Diffuse large B-cell lymphoma  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Hepatic neoplasm  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Non-Hodgkin's lymphoma  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Small cell carcinoma  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Ureteral neoplasm  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Nervous system disorders     
Cerebrovascular accident  1  3/267 (1.12%)  3 1/263 (0.38%)  1
Convulsion  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Dizziness  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Dystonia  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Encephalopathy  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Hypoaesthesia  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Hypoglycaemic seizure  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Metabolic encephalopathy  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Presyncope  1  0/267 (0.00%)  0 1/263 (0.38%)  2
Syncope  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Tension headache  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Transient ischaemic attack  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous  1  2/84 (2.38%)  4 1/95 (1.05%)  1
Hyperemesis gravidarum  1  1/84 (1.19%)  1 0/95 (0.00%)  0
Pregnancy  1  1/84 (1.19%)  1 0/95 (0.00%)  0
Psychiatric disorders     
Agitation  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Bipolar disorder  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Major depression  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Renal and urinary disorders     
Hydronephrosis  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Nephrolithiasis  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Polyuria  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Renal failure acute  1  3/267 (1.12%)  6 8/263 (3.04%)  9
Renal failure chronic  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Tubulointerstitial nephritis  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Reproductive system and breast disorders     
Ovarian cyst ruptured  1  0/84 (0.00%)  0 1/95 (1.05%)  1
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Asthma  1  2/267 (0.75%)  2 1/263 (0.38%)  1
Cough  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Dyspnoea  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Pulmonary embolism  1  1/267 (0.37%)  1 1/263 (0.38%)  1
Pulmonary mass  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Skin and subcutaneous tissue disorders     
Diabetic ulcer  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Hypersensitivity vasculitis  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Skin ulcer  1  2/267 (0.75%)  2 1/263 (0.38%)  1
Surgical and medical procedures     
Amputation  1  2/267 (0.75%)  2 0/263 (0.00%)  0
Arthrodesis  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Debridement  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Gastric bypass  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Insertion of ambulatory peritoneal catheter  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Knee arthroplasty  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Nephrectomy  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Penile prosthesis insertion  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Shoulder operation  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Spinal laminectomy  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Stent placement  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Surgery  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Toe amputation  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Vascular graft  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Vascular disorders     
Accelerated hypertension  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Aneurysm  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Aortic stenosis  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Hypertension  1  1/267 (0.37%)  1 1/263 (0.38%)  1
Leriche syndrome  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Orthostatic hypotension  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Peripheral arterial occlusive disease  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Peripheral vascular disorder  1  0/267 (0.00%)  0 1/263 (0.38%)  1
Shock  1  1/267 (0.37%)  1 0/263 (0.00%)  0
Thrombophlebitis superficial  1  0/267 (0.00%)  0 1/263 (0.38%)  1
1
Term from vocabulary, MedDRA 18.1 to 22.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Allopurinol Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   121/267 (45.32%)      119/263 (45.25%)    
General disorders     
Influenza like illness  1  17/267 (6.37%)  20 14/263 (5.32%)  14
Infections and infestations     
Bronchitis  1  10/267 (3.75%)  10 22/263 (8.37%)  27
Sinusitis  1  16/267 (5.99%)  18 13/263 (4.94%)  16
Upper respiratory tract infection  1  31/267 (11.61%)  47 30/263 (11.41%)  37
Urinary tract infection  1  17/267 (6.37%)  33 21/263 (7.98%)  36
Nasopharyngitis  1  18/267 (6.74%)  21 20/263 (7.60%)  22
Metabolism and nutrition disorders     
Hypoglycaemia  1  26/267 (9.74%)  33 29/263 (11.03%)  47
Musculoskeletal and connective tissue disorders     
Pain in extremity  1  14/267 (5.24%)  17 16/263 (6.08%)  16
Skin and subcutaneous tissue disorders     
Rash  1  43/267 (16.10%)  58 39/263 (14.83%)  45
1
Term from vocabulary, MedDRA 18.1 to 22.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Alessandro Doria (Sponsor and PI of the study)
Organization: Joslin Diabetes Center
Phone: 617-319-0970
EMail: alessandro.doria@joslin.harvard.edu
Layout table for additonal information
Responsible Party: Alessandro Doria, Joslin Diabetes Center
ClinicalTrials.gov Identifier: NCT02017171    
Obsolete Identifiers: NCT01575379
Other Study ID Numbers: DK101108
UC4DK101108-01 ( U.S. NIH Grant/Contract )
First Submitted: December 16, 2013
First Posted: December 20, 2013
Results First Submitted: October 7, 2020
Results First Posted: November 20, 2020
Last Update Posted: December 4, 2020