Study With Deferiprone and/or Desferrioxamine in Iron Overloaded Patients

November 16, 2012 updated by: Lipomed

Randomized Open-label Phase III Study With Deferiprone and/or Desferrioxamine in Iron Overloaded Patients

Comparison of efficacy and toxicity of the combination treatment of deferiprone and desferrioxamine with the single agent treatment of either drug

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients with refractory anemias requiring regular blood transfusions accumulate iron at the rate of approximately 0.5 mg/kg/day, which may lead to serious organ toxicity. The human body has no active mechanism for the excretion of excess iron. Therefore multiply transfused patients will develop a secondary hemosiderosis, if no iron excretion is achieved by a chelating agent. Symptoms of iron-overload occur when body iron stores reach 10-20 g. At higher levels severe, even fatal complications, particularly cardiac failure, may develop.

Desferrioxamine (DFO, Desferal) is the established and commonly used iron-chelating drug, but is expensive and must be given by slow subcutaneous or intravenous infusion for 8-12 hours a day during 5-7 days weekly at a dosage of 40-50mg/kg body weight/day. This often leads to failure of compliance of the patient and therefore to inefficient iron chelation. Further some patients are hypersensitive to desferrioxamine and others suffer from toxicity, e.g. to the ears or eyes.

Deferiprone (L1; CP20; 1,2 dimethyl-3-hydroxy-pyrid-4-one) is an orally active iron chelator investigated in various clinical trials since 1987. Dosages of 75 - 100mg/kg body weight/day of L1 have been found effective to maintain stable iron balance (urinary iron excretion of 0.5mg/kg/day) and to reduce serum ferritin levels between 6% and 25% within one year of treatment in iron-overloaded thalassemic patients. There exists long-term experience with patients who have received deferiprone continuously for more than 10 years so far. However, only few controlled comparison studies with L1 and DFO have been performed so far in order to confirm the effectiveness of deferiprone.

The main side effects encountered during a deferiprone therapy are arthropathy, gastrointestinal symptoms, headache, and mild zinc deficiency. These adverse effects are usually reversed on reducing the dose or discontinuing the drug. Except for severe joint symptoms in few patients, most of the subjects in different clinical trials have been able to continue with L1 therapy for a long-term. The most severe and rare complication following L1 administration is agranulocytosis or neutropenia.

A new treatment regimen by combining deferiprone with desferrioxamine is currently being investigated in many countries. Preliminary data could demonstrate that the combined use of both drugs is highly active showing a synergistic or even additive effect (significant decrease of serum ferritin and hepatic iron content, increase of urinary iron excretion). This synergism could be explained by the different mode of activity of the two drugs. It could be demonstrated that patients who were not sufficiently chelated with desferrioxamine or deferiprone, could achieve a negative iron balance with the combination treatment of both drugs. The combined regimen was generally well-tolerated and there is evidence that the individual toxicity profile of both drugs can be positively influenced by the simultaneous administration of L1 and DFO. The daily treatment with L1 tablets combined with a twice a week administration of parenteral desferrioxamine is more patient-convenient and therefore may enhance the compliance of the patient. In addition, this new treatment regimen will reduce the overall therapy expenses if compared to the high Desferal and material costs related to the parenteral administration of DFO on 5 to 7 days per week.

The results of the previous studies with deferiprone are often not comparable, e.g. laboratory parameters, toxicities and side effects vary from study to study. The number of patients included in the clinical investigations was in general too low to allow statistically significant evaluations. Further, there is no controlled randomized study comprising an appropriate number of patients in order to allow a comparison between the combination arm and the single agent control arms. This study protocol aims to evaluate the feasibility of the combination treatment by comparing the efficacy and safety of the combined drugs with the single agent treatment of L1 and DFO in iron-overloaded patients with thalassemia or refractory anemia in a controlled randomized multicenter study.

Study Type

Interventional

Enrollment (Actual)

95

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Cairo, Egypt
        • Pediatric Hospital, Cairo University
  • Turkey
    • Izmir
      • Bornova, Izmir, Izmir, Turkey, 35100
        • Ege University Medical School

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Iron-overloaded patients without prior iron chelation therapy as well as pretreated patients
  • Age: 4 years and older
  • Sex: male and female
  • Written informed consent

Exclusion Criteria:

  • Children < 4 years of age
  • Patients non-compliant to DFO or L1
  • Patients with known DFO or L1 toxicity/intolerance
  • Neutropenia (neutrophils < 1.5 x 10exp9/L)
  • Thrombocytopenia (platelets < 100 x 10exp9/L)
  • Renal, hepatic (liver enzymes 2.5x of upper normal level and higher) or decompensated heart failure
  • Active viral illness currently treated with interferon-alpha/ribavirin
  • Patients with repeated Yersinia infections
  • HIV-positivity
  • Pregnancy and nursing
  • Female and male of reproductive age planning for family, sexually active but not taking adequate contraceptive precaution

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Deferiprone + Desferrioxamine
Drug: Deferiprone (L1)
75 mg/kg body weight daily
Drug: Desferrioxamine
In combination with deferiprone: 40-50 mg/kg body weight 2-times weekly As single agent: 40-50 mg/kg body weight 5- to 7-times weekly
Experimental: Deferiprone single agent
Drug: Deferiprone (L1)
75 mg/kg body weight daily
Active Comparator: Desferrioxamine single agent
Drug: Desferrioxamine
In combination with deferiprone: 40-50 mg/kg body weight 2-times weekly As single agent: 40-50 mg/kg body weight 5- to 7-times weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Clinical efficacy (Iron balance and liver iron concentration)
Time Frame: At baseline and at 12 months
At baseline and at 12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Safety profile (general, hematologic, and organ toxicity)
Time Frame: At 3-monthly intervals
At 3-monthly intervals
Liver histology
Time Frame: At baseline and at 12 months
At baseline and at 12 months
Quality of life (patient's subjective of compliance and tolerance)
Time Frame: At 3-monthly intervals
At 3-monthly intervals
Actual treatment duration (ATD)
Time Frame: At 12 months
At 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lipomed

Investigators

  • Principal Investigator: Amal M El-Beshlawy, Prof. Dr., Pediatric Hospital, Cairo University, Cairo, Egypt
  • Principal Investigator: Yesim Aydinok, Prof. Dr., EGE University Medical School Bornova, Izmir, Turkey

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2002

Study Registration Dates

First Submitted

July 10, 2006

First Submitted That Met QC Criteria

July 10, 2006

First Posted (Estimate)

July 11, 2006

Study Record Updates

Last Update Posted (Estimate)

November 19, 2012

Last Update Submitted That Met QC Criteria

November 16, 2012

Last Verified

November 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DF-1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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