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Effect of Deferasirox on Endocrine Complications in Subjects With Transfusion Dependent Thalassemia (CENTAurus)

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ClinicalTrials.gov Identifier: NCT02069886
Recruitment Status : Withdrawn
First Posted : February 24, 2014
Last Update Posted : April 20, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE February 20, 2014
First Posted Date  ICMJE February 24, 2014
Last Update Posted Date April 20, 2017
Study Start Date  ICMJE December 2014
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 20, 2014)
Change from baseline of glucose blood level measured after 2 h after receiving a glucose-equivalent oral challenge [ Time Frame: 36 months ]
The primary efficacy variable is the change (mg/dl) from baseline to 36 months of glucose plasma levels measured 2 hr post glusose equivalent oral challange. After a 12-hour overnight fasting, at zero time (baseline) blood sample will be drawn and afterwards patients will receive a glucose-equivalent oral challenge (75 grams). After glucose loading plasma samples will be drawn at 30, 60, 90, 120 minutes for determination of plasma glucose. This will be repeated every 6 month till end of study
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 20, 2014)
  • Glucose of OGTT ( AUC) [ Time Frame: baseline and every 6 months measurement of 2hour Glocose of OGTT ]
    change in of glucose metabolism during deferasirox treatment measuring the change versus baseline of 2-hr and fasting glucose plasma level of OGTT.After a 12-hour overnight fasting, at zero time (baseline) blood sample will be drawn and afterwards patients will receive a glucose-equivalent oral challenge (75 grams). After glucose loading plasma samples will be drawn at 30, 60, 90, 120 minutes for determination of plasma glucose . This will be repeated every 6 months till end of study
  • change on insulin secretion and sensitivity [ Time Frame: baseline and every 6 months measurement of 2hr Glucose OGTT ]
    Change in insulin secretion and insulin sensitivity at every measurement versus screening. Stumvol Formula will be applied to values of 2hr glucose OCTT to calucolate insulin secretion and insulin sensitivity. After a 12-hour overnight fasting, at zero time (baseline) blood sample will be drawn and afterwards patients will receive a glucose-equivalent oral challenge (75 grams). After glucose loading plasma samples will be drawn at 30, 60, 90, 120 minutes for determination of insulin concentration.
  • Measurement of thyroid hormones TSH and FT4 [ Time Frame: baseline and every 12 months ]
    Changes in plasma levels of TSH and FT4 at every measurement versus screening. Blood samples will be drawn from the patient at baseline and every 12 month till end of study and plansa concentration of thyroid hormons TSH and FT4 will be assessed.
  • Risk factors for the impairment of glucose homeostasis [ Time Frame: baseline and monthly till End of Study ]
    information on age, sex, ethnicity, BMI, metabolic syndrome (hypertension, dyslipidemia, hypertrygliceridemia), chronic use of steroids, use of immunosuppressive drugs, growth hormonal deficit will be collected on a monthly basis till end of study
  • Changes in endocrine funcionts parameters [ Time Frame: baseline and monthly till EOS ]
    - Female patients will be assessed for the presence or absence of menses every month versus baseline .Use of current hormonal replacing therapy, if any (e.g. thyroxin therapy for patients with non-compensated hypothyroidism, hormonal replacement drugs for hypogonadal patients) will be checked on a monthly basis versus baseline
  • Changes in parameters of bone metabolism [ Time Frame: baseline, monthly or every 6 months till end of study ]
    - Blood samples wiil be drawn to measure levels of serum calcium, phosphorus, alkaline phosphatase, vitamin D levels (25-hydroxycholecalciferol), serum calcium, parathormone (intact 1-84 PTH) from baseline to the end of study. Blood samples will be drawn to assess also Vitamin D and parathormone at baseline and then every six months. The intact parathormone will be assessed by evaluating the 1-84 PTH form. Inorganic phosphorus, serum calcium will be assessed at baseline and then monthly; alkaline phosphatase will be evaluated at baseline, every two weeks during the first month of treatment and monthly thereafter till EOS.
  • Iron overload status [ Time Frame: baseline and regularly till end of study (monthly or yearly as specified) ]
    Blood samples will be drawn to assess Serum Ferriting. Liver and cardiac iron will be assessed by MRI (MRI R2 annual measurements for liver, MRI T2* annual measurements for cardiac); -Relationship between changes in SF, LIC and cardiac T2* and changes in primary (OGTT) and secondary endpoints (glucose metabolism trend, insulin secretion and insulin sensitivity);
  • Safety of deferasirox therapy [ Time Frame: baseline and at every scheduled visit (weekly for the first months or after dose escalation and monthly thereafter or yearly till EOS ]
    Clinical and laboratory monitoring of AEs and SAEs (in particular changes in hepatic, renal, audiometric and ophthalmology parameters). Blood samples will be drawn to assess liver functions, renal funtions. Urine test will be performed to assess renal functions. An audiometric and ophalmologic visit will be done to assess eyes and ears functions.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Deferasirox on Endocrine Complications in Subjects With Transfusion Dependent Thalassemia
Official Title  ICMJE A Multicenter, Open-label, Single Arm, Interventional Phase IV Study, to Evaluate the Effect of Deferasirox on Endocrine Complications in Subjects With Transfusion Dependent Thalassemia
Brief Summary The CENTAurus trial is a prospective clinical study designed to address systematically some of the relevant endocrine complications in an iron overloaded thalassemic population, primary objective being the assessment of the effect of deferasirox therapy on glucose metabolism/homeostasis. Other endocrine parameters complementary or supportive to the primary objective will be assessed and analyzed during this study. A number of lab parameters related to other axes of the endocrine system will be collected and analyzed.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE Thalassemia (Transfusion Delendent)
Intervention  ICMJE Drug: deferasirox
125, 250, 500 mg dispersable tablets
Study Arms  ICMJE Experimental: deferasirox
single arm. all patients will receive deferasirox
Intervention: Drug: deferasirox
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: October 19, 2014)
0
Original Estimated Enrollment  ICMJE
 (submitted: February 20, 2014)
40
Estimated Study Completion Date  ICMJE December 2018
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

1. Beta thalassemia major and severe intermedia patients transfusion dependent and with transfusional iron overload 2. Patients with diagnosis of impaired fasting glucose or impaired glucose tolerance 4.Patients naïve to deferasirox or patients who already receive deferasirox at sub-optimal doses 5.Cardiac MRI T2* >10 msec; 7.normal cardiac function (LVEF > 56%);

Exclusion Criteria:

  1. Non transfusional hemosiderosis;
  2. Patients with diabetes mellitus (genetic or secondary) or history of diabetes mellitus in 1st degree relatives;

4.Patients who received organ transplant; 5.Patients with galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption; 6.Patients unable to tolerate (or who have unacceptable toxicities to) prior treatment with deferasirox; 7.History of hypersensitivity to the study drug or any of its excipients; 8. Renal impairment 10. Liver impairment; 11.Patients with active chronic hepatitis B infection, active hepatitis C infection;

Other protocol-defined inclusion/exclusion criteria may apply" at the end

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Italy
 
Administrative Information
NCT Number  ICMJE NCT02069886
Other Study ID Numbers  ICMJE CICL670AIT12
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP