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CompletedNCT01825512Updated May 4, 2021Results posted

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

A Phase 3 interventional study of Deferiprone and Deferasirox in Chronic Iron Overload, sponsored by Consorzio per Valutazioni Biologiche e Farmacologiche. Completed at 22 sites in 7 countries. Open to participants aged 1 Month to 17 Years. Per ClinicalTrials.gov, last updated 2021-05-04.

Sponsored by Consorzio per Valutazioni Biologiche e Farmacologiche · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
435
Allocation
Randomized
Ages
1 Month to 17 Years
Sex
All
01

Study summary

Multicentre, randomised, open label, non-inferiority active-controlled trial to evaluate efficacy and safety of a 12-months treatment with deferiprone (DFP) at dose of 75-100 mg/kg/day versus deferasirox (DFX) at dose of 20-40 mg/kg/day in paediatric patients (1 month \< 18 years old) affected by hereditary haemoglobinopathies and requiring frequent transfusions and chelation.

Read the detailed description

Haemoglobinopathies are a group of inherited disorders characterized by structural variations of the haemoglobin molecule. Most of the patients affected require for survival chronic red blood cells transfusions to overcome ineffective erythropoiesis. Unfortunately, all chronically transfused patients become clinically iron overloaded as there is no physiological mechanism for the removal of iron from the body. The pathologic changes and clinical manifestations associated to chronic iron overload are common among all transfusional iron-overload patients, albeit best documented in patients with beta-thalassemia major. The recommended treatment consists in regular blood transfusions combined with chelating therapy to remove the harmful iron accumulation in the body.

Currently, in the clinical practice particularly in children and adolescents, the criteria leading to the choice of the chelating agent include also the adherence to therapy, thus favouring the use of oral chelators (Ceci A et al., 2011) DFP (Deferiprone) was the first oral chelator authorised in Europe in 1999 as second line treatment for the treatment of iron overload in patients with thalassaemia major when DFO (Deferoxamine) is contraindicated or inadequate. However, despite a wide experience of DFP with iron overloaded (specifically thalassaemic )patients, limited data are available for younger children. For this reason the need for additional data in younger children is expressively included in the 2009 PDCO (Paediatric Committee) Priority List.

The purpose of this study is to assess the non-inferiority of DFP compared to DFX (deferasirox)in paediatric patients affected by hereditary haemoglobinopathies requiring chronic transfusions and chelation. Non inferiority will be established in terms of percentage of patients successfully chelated, as assessed by serum ferritin levels (in all patients) and cardiac MRI T2* (in patients above 10 years of age able to have an MRI scan without sedation).

02

Conditions studied

  • Chronic Iron Overload

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Keywords

  • chronic iron overload
  • hereditary haemoglobinopathy
  • beta thalassaemia major
  • chelating agents
  • deferiprone
  • deferasirox
  • children
  • paediatrics
03

In context

beta-Thalassemia

294 studies on the registry are indexed under beta-Thalassemia; 69 are open to participants now.

This study's enrollment of 435 is above the median of 40 across 208 interventional studies indexed under beta-Thalassemia.

Browse beta-Thalassemia studies →

Lead sponsor

Consorzio per Valutazioni Biologiche e Farmacologiche is the lead sponsor of 2 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
1 Month to 17 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Patients of both genders aged from 1 month up to less than 18 years at the time of enrolment
  • Patients affected by any hereditary haemoglobinopathy requiring chronic transfusion therapy and chelation, including but not limited to thalassemia syndromes and sickle cell disease
  • Patients on current treatment with deferoxamine (DFO) or DFX or DFP in a chronic transfusion program receiving at least 150 mL/kg/year of packed red blood cells (corresponding approximately to 12 transfusions);
  • For patients naïve to chelation treatment: patients that have received at least 150 mL/kg of packed red blood cells (corresponding to approximately 12 transfusions) in a chronic transfusion program and with serum ferritin levels ≥ 800 ng/mL;
  • Until availability of results from the PK Study (Study DEEP-1, EudraCT n. 2012-000658-67) for patients aged from 1 month to less than 6 years: known intolerance or to DFO;
  • Written and patient's informed assent, relating to his/her comprehension abilities and level of maturity

Exclusion criteria

Exclusion Criteria:

  • Patients with intolerance or known to either DFP or DFX
  • Patients receiving DFX at a dose > 40 mg/kg/day or DFP at a dose > 100 mg/kg/day at screening
  • count \<100.000/mm3 during the run-in phase
  • Absolute neutrophils count \<1.500/mm3 during the run-in phase
  • levels lower than 8g/dL during the run-in phase
  • Evidence of abnormal liver function
  • Iron overload from causes other than transfusional haemosiderosis
  • Severe heart dysfunction secondary to iron overload
  • Serum creatinine level > (Upper Limit of Normal) for age during the run-in phase
  • History of significant medical or psychiatric disorder
  • The patient has received another drug within 30 days prior to this clinical trial
  • Fever and other signs/symptoms of infection in the 10 days before baseline assessment
  • Concomitant use of trivalent cation-dependent medicinal products such as aluminium-based antacids
  • Positive test for β-HCG (Human chorionic gonadotropin) and lactating female patients
Terms in these criteria, in plain language(6)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
435 participants (actual)

Study arms

  • Experimental
    Deferiprone

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

    Drug: Deferiprone

  • Active comparator
    Deferasirox

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

    Drug: Deferasirox

Interventions

  • DrugDeferiprone

    Deferiprone 80 mg/mL oral solution

    Also known as: DFP

  • DrugDeferasirox

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

    Also known as: DFX, ATC Code:V03AC03

06

What researchers measure

Primary outcomes

  1. Percentage of Successfully Chelated Patients

    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

Secondary outcomes

  1. Liver MRI

    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

  2. Cardiac MRI T2*

    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

  3. Ferritin Level

    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

07

Results

Posted Apr 8, 2021

Participant flow

Baseline
Participant flow — Baseline
MilestoneDeferiproneDeferasirox
Started194199
Completed193197
Not completed12
Treatment
Participant flow — Treatment
MilestoneDeferiproneDeferasirox
Started193197
Completed140170
Not completed5327

Outcome measures

PrimaryPercentage of Successfully Chelated Patients

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
Reported as:
Count of participants · Participants
Percentage of Successfully Chelated Patients
ParticipantsDeferiproneDeferasirox
Percentage of Successfully Chelated Patients6980
Statistical analysis
  • Deferiprone vs Deferasirox · Treatment success rate: -12.5
SecondaryLiver MRI

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
Reported as:
Mean · mg/g
Liver MRI
mg/gDeferiproneDeferasirox
Liver MRI-0.848 ± 0.887-2.975 ± 0.776
Statistical analysis
  • Deferiprone vs Deferasirox · ANCOVA · p = 0.074 · Mean difference (final values): 2.128 · 95% CI -0.213 to 4.468
SecondaryCardiac MRI T2*

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
Reported as:
Mean · milliseconds (ms)
Cardiac MRI T2*
milliseconds (ms)DeferiproneDeferasirox
Cardiac MRI T2*0.488 ± 1.2841.121 ± 1.169
Statistical analysis
  • Deferiprone vs Deferasirox · ANCOVA · p = 0.717 · Mean difference (final values): -0.633 · 95% CI -4.085 to 2.819
SecondaryFerritin Level

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
Reported as:
Mean · ng/mL
Ferritin Level
ng/mLDeferiproneDeferasirox
Ferritin Level-397.583 ± 121.794-398.184 ± 110.619
Statistical analysis
  • Deferiprone vs Deferasirox · GLM · p = 0.997 · Mean difference (final values): 0.601 · 95% CI -323.580 to 324.781

Adverse events

Collected over through study completion, an average of 1 year for subject. Non-serious events are listed at a 4% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Deferiprone0/193 (0%)13/193 (6.7%)152/193 (78.8%)
Deferasirox0/197 (0%)14/197 (7.1%)89/197 (45.2%)
Most frequent serious events
Showing 10 of 22
Most frequent serious events
EventDeferiproneDeferasirox
agranulocytosisBlood and lymphatic system disorders3/1930/197
neutropeniaBlood and lymphatic system disorders2/1930/197
hypertransaminasaemiaHepatobiliary disorders2/1931/197
pneumoniaInfections and infestations2/1931/197
sickle cell anaemia with crisis subjects affected/exposedBlood and lymphatic system disorders0/1932/197
chest painGeneral disorders0/1932/197
acute kidney injuryRenal and urinary disorders0/1932/197
testicular injuryInjury, poisoning and procedural complications1/1930/197
splenectomySurgical and medical procedures1/1930/197
seizureNervous system disorders1/1930/197
Most frequent other events
Most frequent other events
EventDeferiproneDeferasirox
vomitingGeneral disorders33/1938/197
pyrexiaGeneral disorders28/19332/197
arthralgiaMusculoskeletal and connective tissue disorders23/1935/197
abdominal painGeneral disorders20/1938/197
neutropeniaBlood and lymphatic system disorders18/19311/197
coughRespiratory, thoracic and mediastinal disorders15/19316/197
pharyngitisInfections and infestations15/1939/197

Baseline characteristics

Age, Customized
Age, Customized(participants)DeferiproneDeferasiroxTotal
<6 years5958117
> or equal to 6 years and <10 years474794
> or equal to 10 years8792179
Sex: Female, Male
Sex: Female, Male(Participants)DeferiproneDeferasiroxTotal
Female8093173
Male113104217
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)DeferiproneDeferasiroxTotal
Europe5656112
North Africa121122243
Rest of Africa6511
Asia011
North America000
Latin America000
Other5611
Missing5712
Region of Enrollment
Region of Enrollment(participants)DeferiproneDeferasiroxTotal
United Kingdom111223
Italy302858
Tunisia282856
Egypt9699197
Albania192039
Greece5611
Cyprus448
Ferritin level
Ferritin level(ng/ml)DeferiproneDeferasiroxTotal
Mean2756 ± 21752989 ± 24092876 ± 2298
08

Study locations

22 sites
  • Hospital 'Ihsan Çabej'
    Lushnjë, Albania
  • Qendra Spitalore Universitare "Nene Tereza" Tirane
    Tirana, Albania
  • Department of Medical and Public health Services of the Ministry of Health
    Nicosia, Cyprus
  • Alexandria University Hospital - Faculty of Medicine
    Alexandria, Egypt
  • Cairo University Faculty of Medicine
    Cairo, Egypt
  • Zagazig University Hospitals
    Zagazig, Egypt
  • National And Kapodistrian University of Athens
    Athens, Greece
  • Centro di Thalassemia, Ospedale Civile di Lentini
    Lentini, SR, Italy
  • Università di Bari - Facoltà di Medicina
    Bari, Italy
  • ASL Cagliari Ospedale Regionale per le Microcitemie
    Cagliari, Italy
  • Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi
    Catania, Italy
  • Presidio Ospedaliero "Annunziata", Centro di Studi della Microcitemia
    Cosenza, Italy
  • A.O.Universitaria Meyer
    Firenze, Italy
  • Clinica Pediatrica Policlinico di Modena
    Modena, Italy
  • Azienda Ospedaliera di Rilievo Nazionale "Antonio Cardarelli"
    Napoli, Italy
  • Azienda Ospedaliera di Padova
    Padova, Italy
  • Ospedali Riuniti Villa Sofia - Cervello
    Palermo, Italy
  • U.O.C. Ematologia - Emoglobinopatie, Ospedale G. Di Cristina
    Palermo, Italy
  • Clinica Pediatrica Università - ASL 1 D.H per Talassemia
    Sassari, Italy
  • Centre National de Greffe de Moelle Osseuse Tunis
    Tunis, Tunisia
  • Barts Health NHS Trust
    London, United Kingdom
  • Queen's Hospital
    Romford, United Kingdom
09

References and documents

Publications

  • Giannuzzi V, Felisi M, Bonifazi D, Devlieger H, Papanikolaou G, Ragab L, Fattoum S, Tempesta B, Reggiardo G, Ceci A. Ethical and procedural issues for applying researcher-driven multi-national paediatric clinical trials in and outside the European Union: the challenging experience of the DEEP project. BMC Med Ethics. 2021 Apr 29;22(1):49. doi: 10.1186/s12910-021-00618-2. PubMed 33926431 ↗
  • Maggio A, Kattamis A, Felisi M, Reggiardo G, El-Beshlawy A, Bejaoui M, Sherief L, Christou S, Cosmi C, Della Pasqua O, Del Vecchio GC, Filosa A, Cuccia L, Hassab H, Kreka M, Origa R, Putti MC, Spino M, Telfer P, Tempesta B, Vitrano A, Tsang YC, Zaka A, Tricta F, Bonifazi D, Ceci A. Evaluation of the efficacy and safety of deferiprone compared with deferasirox in paediatric patients with transfusion-dependent haemoglobinopathies (DEEP-2): a multicentre, randomised, open-label, non-inferiority, phase 3 trial. Lancet Haematol. 2020 Jun;7(6):e469-e478. doi: 10.1016/S2352-3026(20)30100-9. PubMed 32470438 ↗

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Mar 2014 to primary completion in Sep 2017, 42 months.

Results were first posted in Apr 2021, 3 years 6 months after primary completion.

Of 18 phase 3 interventional studies under beta-Thalassemia, half reached primary completion within 60 months of starting (the median), counting those still running; a quarter within 22 and three quarters within 67. This study's 42 months is below that.

How these figures are worked out, and which studies are left out of them.

Registered
Apr 3, 2013
First posted
Apr 5, 2013
StartActual
Mar 17, 2014
Primary completionActual
Sep 21, 2017
CompletionActual
Sep 21, 2017
Results first posted
Apr 8, 2021
Last update
May 4, 2021
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on May 4, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01825512
Lead sponsor
Consorzio per Valutazioni Biologiche e Farmacologiche
Collaborators
European Commission
Responsible party
Sponsor
First posted
Apr 5, 2013
Start date
Mar 17, 2014
Primary completion
Sep 21, 2017
Completion
Sep 21, 2017
Results posted
Apr 8, 2021
Last update
May 4, 2021

Study contacts

Donato Bonifazi, Dr
study director · Consorzio per Valutazioni Biologiche e Farmacologiche
Aurelio Maggio, MD
principal investigator · Ospedali Riuniti Villa Sofia-Cervello

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Oct 2017. You cannot join it, but the record below documents what was studied.

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