Phase 4
Completed N=40
Evaluation of the Impact of Renal Function on the Pharmacokinetics of SIKLOS ® (DARH)
Sickle Cell Disease · Renal Function Disorder
Source: ClinicalTrials.gov NCT02522104 ↗
Enrolled (actual)
40
Serious AEs
7.4%
Results posted
Aug 2021
Primary outcomePrimary: Measure of Plasmatic Data: Maximum Concentration (Cmax) — 271.8; 316.8; 260.2 Micromolar
◆ Published Evidence
No publication linked
No peer-reviewed publication reporting this trial's results has been linked yet. This can indicate results are unpublished — a known publication-bias signal. We re-check periodically.
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Measure of Plasmatic Data: Maximum Concentration (Cmax) |
271.8; 316.8; 260.2 | — |
| PRIMARY Measure of Plasmatic Data: Minimum Concentration (Cmin) |
3.80; 4.2; 7.1 | — |
| PRIMARY Measure of Plasmatic Data: Time to Obtain the Maximum Concentration (Tmax) |
0.9; 1.0; 1.0 | — |
| PRIMARY Measure of Plasmatic Data: Area Under the Curve (AUC0-24) |
1144.0; 1384.3; 1580.6 | — |
| PRIMARY Measure of Plasmatic Data: Elimination Half-life (T½) |
4.30; 4.75; 4.98 | — |
| PRIMARY Measure of Plasmatic Data: Total Clearance (Cl Tot) |
10.1; 10.3; 6.4 | — |
| PRIMARY Measure of Plasmatic Data: Distribution Volume |
61.2; 70.3; 44.2 | — |
| PRIMARY Measure of Urinary Data: Hydroxyurea Urinary Fractions |
35.8; 44.3; 20.2 | — |
| PRIMARY Measure of Urinary Data: Renal Clearance (Cl Renal). |
3.9; 4.7; 1.3 | — |
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.
Data sourced from ClinicalTrials.gov (NCT02522104). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.