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Trial record 4 of 5 for:    deep-2

Efficacy/Safety Study of Deferiprone Compared to Deferasirox in Paediatric Patients

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ClinicalTrials.gov Identifier: NCT01825512
Recruitment Status : Completed
First Posted : April 5, 2013
Results First Posted : April 8, 2021
Last Update Posted : May 4, 2021
Sponsor:
Collaborator:
European Commission
Information provided by (Responsible Party):
Consorzio per Valutazioni Biologiche e Farmacologiche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Chronic Iron Overload
Interventions Drug: Deferiprone
Drug: Deferasirox
Enrollment 435
Recruitment Details  
Pre-assignment Details Informed consent was collected for 435 patients that were enrolled in the study, however 42 of them were excluded from the study for the following reasons: 17 did not meet inclusion criteria, 5 withdrew the consent and 20 were lost to follow-up.
Arm/Group Title Deferiprone Deferasirox
Hide Arm/Group Description

75-100 mg/kg/day seven days per week

Deferiprone: Deferiprone 80 mg/mL oral solution

20 to 40 mg/kg/day seven days per week

Deferasirox: Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg

Period Title: Baseline
Started 194 199
Completed 193 197
Not Completed 1 2
Period Title: Treatment
Started 193 197
Completed 140 170
Not Completed 53 27
Arm/Group Title Deferiprone Deferasirox Total
Hide Arm/Group Description

75-100 mg/kg/day seven days per week

Deferiprone: Deferiprone 80 mg/mL oral solution

20 to 40 mg/kg/day seven days per week

Deferasirox: Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg

Total of all reporting groups
Overall Number of Baseline Participants 193 197 390
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
<6 years Number Analyzed 193 participants 197 participants 390 participants
59 58 117
> or equal to 6 years and <10 years Number Analyzed 193 participants 197 participants 390 participants
47 47 94
> or equal to 10 years Number Analyzed 193 participants 197 participants 390 participants
87 92 179
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 193 participants 197 participants 390 participants
Female
80
  41.5%
93
  47.2%
173
  44.4%
Male
113
  58.5%
104
  52.8%
217
  55.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Europe Number Analyzed 193 participants 197 participants 390 participants
56 56 112
North Africa Number Analyzed 193 participants 197 participants 390 participants
121 122 243
Rest of Africa Number Analyzed 193 participants 197 participants 390 participants
6 5 11
Asia Number Analyzed 193 participants 197 participants 390 participants
0 1 1
North America Number Analyzed 193 participants 197 participants 390 participants
0 0 0
Latin America Number Analyzed 193 participants 197 participants 390 participants
0 0 0
Other Number Analyzed 193 participants 197 participants 390 participants
5 6 11
Missing Number Analyzed 193 participants 197 participants 390 participants
5 7 12
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United Kingdom Number Analyzed 193 participants 197 participants 390 participants
11 12 23
Italy Number Analyzed 193 participants 197 participants 390 participants
30 28 58
Tunisia Number Analyzed 193 participants 197 participants 390 participants
28 28 56
Egypt Number Analyzed 193 participants 197 participants 390 participants
96 99 197
Albania Number Analyzed 193 participants 197 participants 390 participants
19 20 39
Greece Number Analyzed 193 participants 197 participants 390 participants
5 6 11
Cyprus Number Analyzed 193 participants 197 participants 390 participants
4 4 8
Ferritin level   [1] 
Mean (Standard Deviation)
Unit of measure:  Ng/ml
Number Analyzed 163 participants 173 participants 336 participants
2756  (2175) 2989  (2409) 2876  (2298)
[1]
Measure Analysis Population Description: The difference is due to missing data at baseline
1.Primary Outcome
Title Percentage of Successfully Chelated Patients
Hide Description Percentage of successfully chelated patients is assessed by serum ferritin levels (in all patients) and cardiac MRI T2* (in patients above 10 years of age able to perform an MRI scan without sedation)
Time Frame at baseline and after 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol population 1 (PP1): number of patients for whom the primary composite efficacy endpoint data were available at baseline and after 1 year of treatment (271 subjects)
Arm/Group Title Deferiprone Deferasirox
Hide Arm/Group Description:

75-100 mg/kg/day seven days per week

Deferiprone: Deferiprone 80 mg/mL oral solution

20 to 40 mg/kg/day seven days per week

Deferasirox: Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg

Overall Number of Participants Analyzed 125 146
Measure Type: Count of Participants
Unit of Measure: Participants
69
  55.2%
80
  54.8%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Deferiprone, Deferasirox
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Deferiprone was declared non inferior to Deferasirox if the lower limit of the 95% confidence interval for the difference in the proportion of successful chelation in the two groups is above -12.5%.
Method of Estimation Estimation Parameter Treatment success rate
Estimated Value -12.5
Confidence Interval (1-Sided) 95%
-12.5
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Liver MRI
Hide Description Change in liver iron concentration (measured using liver MRI), assessed as difference between value at 12 months minus value at baseline.
Time Frame at baseline and after 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol population 3 (PP3): number of patients for whom liver iron concentration were available at baseline and after 1 year of treatment (106 subjects)
Arm/Group Title Deferiprone Deferasirox
Hide Arm/Group Description:

75-100 mg/kg/day seven days per week

Deferiprone: Deferiprone 80 mg/mL oral solution

20 to 40 mg/kg/day seven days per week

Deferasirox: Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg

Overall Number of Participants Analyzed 46 60
Mean (Standard Error)
Unit of Measure: mg/g
-0.848  (0.887) -2.975  (0.776)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Deferiprone, Deferasirox
Comments [Not Specified]
Type of Statistical Test Other
Comments GLM model
Statistical Test of Hypothesis P-Value 0.074
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.128
Confidence Interval (2-Sided) 95%
-0.213 to 4.468
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.18
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Cardiac MRI T2*
Hide Description Change in cardiac iron concentration (measured using cardiac MRI T2*), assessed as difference between value at 12 months minus value at baseline. MRI T2* is a non-invasive method based on gradient echo (GRE) sequences, where T2* represents the spin-spin relaxation times, measured in milliseconds. The faster the curve decreases (ie, the smaller T2*), the greater amount of iron is in the tissue. Treatment success was assessed as follows: if baseline cardiac T2* was less than 20 ms, an increase of 10% or more after 1 year of treatment was defined as treatment success; if baseline cardiac T2* was more than 20 ms, any increase or a decrease of less than 10% after 1 year of treatment was defined as treatment success.
Time Frame at baseline and after 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol population 3 (PP3): number of patients for whom cardiac T2* concentration were available at baseline and after 1 year of treatment (108 subjects)
Arm/Group Title Deferiprone Deferasirox
Hide Arm/Group Description:

75-100 mg/kg/day seven days per week

Deferiprone: Deferiprone 80 mg/mL oral solution

20 to 40 mg/kg/day seven days per week

Deferasirox: Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg

Overall Number of Participants Analyzed 49 59
Mean (Standard Error)
Unit of Measure: milliseconds (ms)
0.488  (1.284) 1.121  (1.169)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Deferiprone, Deferasirox
Comments [Not Specified]
Type of Statistical Test Other
Comments GLM Analysis
Statistical Test of Hypothesis P-Value 0.717
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.633
Confidence Interval (2-Sided) 95%
-4.085 to 2.819
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.741
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Ferritin Level
Hide Description Change in serum ferritin level, assessed as difference between value at 12 months minus value at baseline.
Time Frame at baseline and after 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol population 2 (PP2): number of patients for whom the per-protocol centralised serum ferritin concentration data were available at baseline and after 1 year of treatment (303 subjects, this population was larger than PP1 because PP2 included patients who did not have cardiac T2* data)
Arm/Group Title Deferiprone Deferasirox
Hide Arm/Group Description:

75-100 mg/kg/day seven days per week

Deferiprone: Deferiprone 80 mg/mL oral solution

20 to 40 mg/kg/day seven days per week

Deferasirox: Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg

Overall Number of Participants Analyzed 137 166
Mean (Standard Error)
Unit of Measure: ng/mL
-397.583  (121.794) -398.184  (110.619)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Deferiprone, Deferasirox
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non inferiority of Deferiprone to Deferasirox is tested considering a non-inferiority margin of 400 ng/mL.
Statistical Test of Hypothesis P-Value 0.997
Comments [Not Specified]
Method GLM
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.601
Confidence Interval (2-Sided) 95%
-323.580 to 324.781
Parameter Dispersion
Type: Standard Error of the Mean
Value: 164.734
Estimation Comments [Not Specified]
Time Frame through study completion, an average of 1 year for subject
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Deferiprone Deferasirox
Hide Arm/Group Description

75-100 mg/kg/day seven days per week

Deferiprone: Deferiprone 80 mg/mL oral solution

20 to 40 mg/kg/day seven days per week

Deferasirox: Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg

All-Cause Mortality
Deferiprone Deferasirox
Affected / at Risk (%) Affected / at Risk (%)
Total   0/193 (0.00%)      0/197 (0.00%)    
Hide Serious Adverse Events
Deferiprone Deferasirox
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/193 (6.74%)      14/197 (7.11%)    
Blood and lymphatic system disorders     
agranulocytosis  3 [1]  3/193 (1.55%)  3 0/197 (0.00%)  0
neutropenia  4 [2]  2/193 (1.04%)  2 0/197 (0.00%)  0
sickle cell anaemia with crisis subjects affected/exposed  5 [3]  0/193 (0.00%)  0 2/197 (1.02%)  2
Gastrointestinal disorders     
diarrhoea  10 [4]  0/193 (0.00%)  0 1/197 (0.51%)  1
General disorders     
pyrexia  7 [5]  1/193 (0.52%)  1 1/197 (0.51%)  1
chest pain  8 [6]  0/193 (0.00%)  0 2/197 (1.02%)  2
gait disturbance  9 [7]  0/193 (0.00%)  0 1/197 (0.51%)  1
Hepatobiliary disorders     
hypertransaminasaemia  11 [8]  2/193 (1.04%)  2 1/197 (0.51%)  1
Infections and infestations     
gastroenteritis  14 [9]  0/193 (0.00%)  0 1/197 (0.51%)  1
meningitis meningococcal  15 [10]  0/193 (0.00%)  0 1/197 (0.51%)  1
herpangina  16 [11]  0/193 (0.00%)  0 1/197 (0.51%)  1
pneumonia  17 [12]  2/193 (1.04%)  2 1/197 (0.51%)  1
subcutaneous abscess  18 [13]  0/193 (0.00%)  0 1/197 (0.51%)  1
urinary tract infection  19 [14]  1/193 (0.52%)  1 1/197 (0.51%)  1
herpes virus infection  20 [15]  0/193 (0.00%)  0 1/197 (0.51%)  1
impetigo  21 [16]  0/193 (0.00%)  0 1/197 (0.51%)  1
upper respiratory tract infection  22 [17]  0/193 (0.00%)  0 1/197 (0.51%)  1
Injury, poisoning and procedural complications     
testicular injury  1 [18]  1/193 (0.52%)  1 0/197 (0.00%)  0
Musculoskeletal and connective tissue disorders     
pain in extremity  13 [19]  0/193 (0.00%)  0 1/197 (0.51%)  1
Nervous system disorders     
seizure  6 [20]  1/193 (0.52%)  1 0/197 (0.00%)  0
Renal and urinary disorders     
acute kidney injury  12 [21]  0/193 (0.00%)  0 2/197 (1.02%)  2
Surgical and medical procedures     
splenectomy  2 [22]  1/193 (0.52%)  1 0/197 (0.00%)  0
1
Term from vocabulary, testicular injury
2
Term from vocabulary, splenectomy
3
Term from vocabulary, agranulocytosis
4
Term from vocabulary, neutropenia
5
Term from vocabulary, sickle cell anaemia
6
Term from vocabulary, seizure
7
Term from vocabulary, pyrexia
8
Term from vocabulary, chest pain
9
Term from vocabulary, gait disturbance
10
Term from vocabulary, diarrhoea
11
Term from vocabulary, hypertransaminasaemi
12
Term from vocabulary, acute kidney injury
13
Term from vocabulary, pain in extremity
14
Term from vocabulary, gastroenteritis
15
Term from vocabulary, meningitis meningoco
16
Term from vocabulary, herpangina
17
Term from vocabulary, pneumonia
18
Term from vocabulary, subcutaneous abscess
19
Term from vocabulary, urinary tract infect
20
Term from vocabulary, herpes virus infecti
21
Term from vocabulary, impetigo
22
Term from vocabulary, upper respiratory tr
Indicates events were collected by systematic assessment
[1]
agranulocytosis
[2]
neutropenia
[3]
sickle cell anaemia with crisis subjects affected/exposed
[4]
diarrhoea
[5]
pyrexia
[6]
chest pain
[7]
gait disturbance
[8]
hypertransaminasaemia
[9]
gastroenteritis
[10]
meningitis meningococcal
[11]
herpangina
[12]
pneumonia
[13]
subcutaneous abscess
[14]
urinary tract infection
[15]
herpes virus infection
[16]
impetigo
[17]
upper respiratory tract infection
[18]
testicular injury
[19]
pain in extremity
[20]
seizure
[21]
acute kidney injury
[22]
splenectomy
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 4%
Deferiprone Deferasirox
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   152/193 (78.76%)      89/197 (45.18%)    
Blood and lymphatic system disorders     
neutropenia   18/193 (9.33%)  26 11/197 (5.58%)  15
General disorders     
pyrexia   28/193 (14.51%)  40 32/197 (16.24%)  56
abdominal pain   20/193 (10.36%)  24 8/197 (4.06%)  9
vomiting   33/193 (17.10%)  42 8/197 (4.06%)  10
Infections and infestations     
pharyngitis   15/193 (7.77%)  18 9/197 (4.57%)  11
Musculoskeletal and connective tissue disorders     
arthralgia   23/193 (11.92%)  28 5/197 (2.54%)  5
Respiratory, thoracic and mediastinal disorders     
cough  1 [1]  15/193 (7.77%)  21 16/197 (8.12%)  25
1
Term from vocabulary, cough
Indicates events were collected by systematic assessment
[1]
cough
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Donato Bonifazi
Organization: Consorzio per Valutazioni Biologiche e Farmacologiche
Phone: +393936698076
EMail: ceo@cvbf.net
Layout table for additonal information
Responsible Party: Consorzio per Valutazioni Biologiche e Farmacologiche
ClinicalTrials.gov Identifier: NCT01825512    
Other Study ID Numbers: DEEP-2
First Submitted: April 3, 2013
First Posted: April 5, 2013
Results First Submitted: January 27, 2021
Results First Posted: April 8, 2021
Last Update Posted: May 4, 2021