Evaluation of the Impact of Renal Function on the Pharmacokinetics of SIKLOS ® (DARH)
Condition: Sickle Cell Disease; Renal Function Disorder
MeSH terms: Anemia, Sickle Cell
Intervention: Siklos
Intervention MeSH terms: Hydroxyurea
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pharmacokinetics of Hydroxyurea

Summary:

      The use of hydroxyurea in sickle cell disease patients with glomerular hyperfiltration and
      renal failure requires a specific monitoring and dose adjustment in order to remain within
      the therapeutic interval while limiting the risk of toxicity or therapeutic failure. For this
      reason the investigators propose to compare the pharmacokinetic parameters of hydroxyurea in
      normal-renal function sickle cell patients to those of patients with glomerular
      hyperfiltration or moderate renal failure.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 18 years.

          -  Male or female.

          -  Sickle cell disease (SS or S-β0thal) confirmed by haemoglobin electrophoresis and
             genotyping by deoxyribonucleic acid (DNA) analysis.

          -  Affiliation to a social security system.

          -  Having freely consented in writing after being informed of the objective, programme
             and potential risks incurred.

        These criteria will apply to the 3 groups of sickle cell disease patients according to the
        renal function stage defined by the glomerular filtration rate (GFR) estimated by the
        formula of the Chronic Kidney Disease EPIdemiology (CKD EPI) collaboration without ethnic
        criterion during the last 6 months before inclusion:

          -  Normal-renal function: 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in
             men.

          -  Moderate renal failure: 30 ≤ GFR ≤ 60 mL/min/1.73m2.

          -  Glomerular renal hyperfiltration: GFR > 130 mL/min/1.73m2 in women and GFR > 140
             mL/min/1.73m2 in men.

               -  Treated with hydroxyurea (Siklos®) with a stable dosage for at least one week ± 2
                  days before inclusion in the study and dose administered in the morning at 9:00 ±
                  15 minutes.

        Exclusion Criteria:

          -  Refusal to consent.

          -  Patients that do not comply.

          -  Occurrence of vaso-occlusive crisis in the month prior to the inclusion in the study.

          -  Patients having had an exchange transfusion in the 15 days before inclusion in the
             study.

          -  Patients participating in another clinical trial or in the exclusion period of a
             previous clinical trial.

          -  Patients treated with a diuretic.

          -  Dialysis patient.

          -  Patients with an intercurrent disorder, especially inflammatory, that has not
             recovered for at least one month.

          -  Pregnant or breast-feeding women.

          -  Patients deprived of liberty or under legal protection.

          -  Patients who cannot understand the objective and the course of the study, incapable of
             giving their consent.

          -  In the event of severe hepatic failure.

          -  In the event of severe renal failure (creatinine clearance < 30 ml/min).

          -  Patients who show toxic signs of bone marrow suppression.