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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Normal-renal function | Experimental | Normal-renal function: 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men |
|
| Glomerular hyperfiltration | Experimental | Glomerular renal hyperfiltration: GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men. |
|
| Moderate renal failure | Experimental | Moderate renal failure: 30 ≤ GFR ≤ 60 mL/min/1.73m2 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Siklos | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Measure of Plasmatic Data: Maximum Concentration (Cmax) | Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure | 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours |
| Measure of Plasmatic Data: Minimum Concentration (Cmin) | Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure | 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours |
| Measure of Plasmatic Data: Time to Obtain the Maximum Concentration (Tmax) | Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure | 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours |
| Measure of Plasmatic Data: Area Under the Curve (AUC0-24) | Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure | 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours |
| Measure of Plasmatic Data: Elimination Half-life (T½) | Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure | 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours |
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Inclusion Criteria:
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.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| BARTOLUCCI Pablo, MD | Centre de Référence des Syndromes Drépanocytaires Majeurs, Hôpital Henri-Mondor | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre de Référence des Syndromes Drépanocytaires Majeurs, Hôpital Henri-Mondor | Créteil | France |
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| ID | Title | Description |
|---|---|---|
| FG000 | Normal-renal Function | Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men |
| FG001 | Glomerular Hyperfiltration | Patients with glomerular renal hyperfiltration defined by GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men |
| FG002 | Moderate Renal Failure | Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Normal-renal Function | Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men |
| BG001 | Glomerular Hyperfiltration | Patients with glomerular renal hyperfiltration defined by GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Measure of Plasmatic Data: Maximum Concentration (Cmax) | Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure | Posted | Mean | Standard Deviation | Micromolar | 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours |
|
From the signature of the informed consent form by the patient until 7 days after the end of the follow-up for the study. Duration of participation for each patients : 9 to 40 days depending on the concomitant treatments.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Normal-renal Function | Patients with normal-renal function defined by 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Aplastic anemia | Blood and lymphatic system disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Overdose | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical director | Addmedica | +33 1 72 69 01 86 | corinne.duguet@addmedica.com |
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| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
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| ID | Term |
|---|---|
| D006918 | Hydroxyurea |
| ID | Term |
|---|---|
| D014508 | Urea |
| D000577 | Amides |
| D009930 | Organic Chemicals |
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| Measure of Plasmatic Data: Total Clearance (Cl Tot) |
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure |
| 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours |
| Measure of Plasmatic Data: Distribution Volume | Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure | 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours |
| Measure of Urinary Data: Hydroxyurea Urinary Fractions | Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure | From 0 to 4 hours, 4 to 7.5 hours and 7.5 to 24 hours |
| Measure of Urinary Data: Renal Clearance (Cl Renal). | Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure | From 0 to 4 hours, 4 to 7.5 hours and 7.5 to 24 hours |
| BG002 | Moderate Renal Failure | Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2 |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| OG002 | Moderate Renal Failure | Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2 |
|
|
| Primary | Measure of Plasmatic Data: Minimum Concentration (Cmin) | Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure | Posted | Mean | Standard Deviation | Micromolar | 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours |
|
|
|
| Primary | Measure of Plasmatic Data: Time to Obtain the Maximum Concentration (Tmax) | Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure | Posted | Mean | Standard Deviation | Hour | 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours |
|
|
|
| Primary | Measure of Plasmatic Data: Area Under the Curve (AUC0-24) | Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure | Posted | Mean | Standard Deviation | Hour x Micromolar | 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours |
|
|
|
| Primary | Measure of Plasmatic Data: Elimination Half-life (T½) | Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure | Posted | Mean | Standard Deviation | Hour | 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours |
|
|
|
| Primary | Measure of Plasmatic Data: Total Clearance (Cl Tot) | Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure | Posted | Mean | Standard Deviation | Liter/Hour | 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours |
|
|
|
| Primary | Measure of Plasmatic Data: Distribution Volume | Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure | Posted | Mean | Standard Deviation | Liter | 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours |
|
|
|
| Primary | Measure of Urinary Data: Hydroxyurea Urinary Fractions | Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure | Posted | Mean | Standard Deviation | Percentage urinary excretion | From 0 to 4 hours, 4 to 7.5 hours and 7.5 to 24 hours |
|
|
|
| Primary | Measure of Urinary Data: Renal Clearance (Cl Renal). | Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure | Posted | Mean | Standard Deviation | Liter/Hour | From 0 to 4 hours, 4 to 7.5 hours and 7.5 to 24 hours |
|
|
|
| 0 |
| 10 |
| 1 |
| 10 |
| 2 |
| 10 |
| EG001 | Glomerular Hyperfiltration | Patients with glomerular renal hyperfiltration defined by GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men. | 0 | 12 | 0 | 12 | 0 | 12 |
| EG002 | Moderate Renal Failure | Patients with moderate renal failure defined by 30 ≤ GFR ≤ 60 mL/min/1.73m2 | 0 | 5 | 1 | 5 | 0 | 5 |
| Hypotension | Cardiac disorders | Non-systematic Assessment |
|
| Vaso-occlusive crisis | Vascular disorders | Non-systematic Assessment |
|
| Fever | General disorders | Non-systematic Assessment |
|
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| D006425 |
| Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |