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RECRUITINGPhase 2INTERVENTIONAL

Losartan for Diffuse Myocardial Fibrosis in Sickle Cell Disease

Losartan for Diffuse Myocardial Fibrosis in Sickle Cell Disease: A Prospective, Phase II Study.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

This study is a pilot, phase II, open-label study of the angiotensin II receptor blocker, losartan, in patients with Sickle Cell Disease (SCD) 6 years or older for 12 months. The investigators will enroll 24 patients with SCD over the course of 1 year with a goal to complete all study procedures in 2 years. The short-term goal is to obtain clinical pilot data regarding the safety and efficacy of losartan in stabilizing or decreasing extracellular volume fraction (ECV) after 12 months of therapy.

Who May Be Eligible (Plain English)

Who May Qualify: 1. 6 years old or older 2. Diagnosis of HbSS or Sbeta0-thalassemia 3. Ability to cooperate with and undergo CMR without sedation or anesthesia 4. Ability to cooperate with and undergo echocardiogram without sedation or anesthesia 5. Patients who are on a stable dose of sickle cell disease-modifying therapy: Hydroxyurea, Voxelotor, L-Glutamine, or Crizanlizumab, for 3 months prior to enrollment will be eligible. Who Should NOT Join This Trial: 1. Current chronic transfusion therapy. Patients who received a simple transfusion for an acute event will be eligible 3 months after completion of transfusion 2. SCD genotypes other than specified in inclusion criteria 3. Any contraindication to CMR such as metallic implants 4. Inability to cooperate with CMR or echocardiography imaging 5. Known congenital heart disease 6. Estimated GFR ≤ to 30 mL/min/1.73 m2 by creatinine clearance 7. Pregnant or lactating females or females of child-bearing potential who are unable to use a medically accepted form of contraception throughout the study 8. Treatment with a renin-angiotensin pathway inhibitor during the 2 weeks prior to enrollment 9. Hypersensitivity to angiotensin receptor II blockers 10. Hyperkalemia (K\>5.5 mEq/L) on a non-hemolyzed sample despite low-potassium diet 11. Hepatic dysfunction defined as serum ALT \> 5x the upper normal limit for age 12. Current lithium therapy 13. Chronic daily use of NSAID 14. HIV infection. Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: 1. 6 years old or older 2. Diagnosis of HbSS or Sbeta0-thalassemia 3. Ability to cooperate with and undergo CMR without sedation or anesthesia 4. Ability to cooperate with and undergo echocardiogram without sedation or anesthesia 5. Patients who are on a stable dose of sickle cell disease-modifying therapy: Hydroxyurea, Voxelotor, L-Glutamine, or Crizanlizumab, for 3 months prior to enrollment will be eligible. Exclusion Criteria: 1. Current chronic transfusion therapy. Patients who received a simple transfusion for an acute event will be eligible 3 months after completion of transfusion 2. SCD genotypes other than specified in inclusion criteria 3. Any contraindication to CMR such as metallic implants 4. Inability to cooperate with CMR or echocardiography imaging 5. Known congenital heart disease 6. Estimated GFR ≤ to 30 mL/min/1.73 m2 by creatinine clearance 7. Pregnant or lactating females or females of child-bearing potential who are unable to use a medically accepted form of contraception throughout the study 8. Treatment with a renin-angiotensin pathway inhibitor during the 2 weeks prior to enrollment 9. Hypersensitivity to angiotensin receptor II blockers 10. Hyperkalemia (K\>5.5 mEq/L) on a non-hemolyzed sample despite low-potassium diet 11. Hepatic dysfunction defined as serum ALT \> 5x the upper normal limit for age 12. Current lithium therapy 13. Chronic daily use of NSAID 14. HIV infection.

Treatments Being Tested

DRUG

Losartan

Losartan dosing for participants \<16 years will be 0.7 mg/kg (maximum of 50 mg) once daily. The dose can be increased to 1.4 mg/kg (maximum of 100 mg once daily) after 2 weeks if the dose was tolerated (no hypotension or hyperkalemia). For patients ≥16 years, the starting dose will be 50 mg once daily which can be increased to 100 mg daily if tolerated after 2 weeks.

Locations (1)

Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States