Losartan to Reverse Sickle Nephropathy

NCT01479439 | Completed Phase 2 Results DMC

• 1 other identifier: 2010-3070
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 9

Brief Summary

Sickle cell disease causes kidney damage with increasing age, leading to chronic kidney disease and renal failure in nearly one third of patients with sickle cell disease. Currently, there is no treatment for sickle cell related kidney disease.

Conditions

Nephropathy; Sickle Cell Anemia

Outcome Measures

Primary Outcomes (1)

• Categorical Change in Urinary Albumin-to-creatinine Ratio (UACR) From Baseline

  Number of participants who have a ≥25% reduction in urinary albumin-to-creatinine ratio (UACR) from baseline to 6 months. This is a categorical outcome (yes/no). We hypothesized and pre-specified that ≥30% of the subjects in the microalbuminuria group would meet this outcome.

  Baseline and 6 months

Secondary Outcomes (2)

• Change in UACR

  Baseline and 6 months

• Change in Creatinine Clearance

  Baseline and 6 months

Study Arms (1)

Sickle cell disease

EXPERIMENTAL

The purpose of this research study is to see if losartan can help reduce or reverse damage done to the kidneys of children and adults with Sickle Cell Anemia (SCA) and Sickle Beta-zero (HbSβ0) Thalassemia.

Drug: Losartan

Interventions

Losartan DRUG

Form: suspension, tablet. Dosage \& frequency: age 6-16 = 0.7mg/kg once daily; age \>16 = 50mg once daily. Duration: 6 months

Sickle cell disease

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥6 years of age; for no albuminuria (NoA) group age is ≥ 6 years and \<21 years of age
• Diagnosis of hemoglobin SS disease or Sβ0 thalassemia by hemoglobin electrophoresis and/or β-globin gene mapping.
• Urine osmolality \<700 mOsm (milliosmoles) on first morning urine
• Written informed consent (and assent, where applicable)
• Documented urine albumin to creatinine ratio (UACR) showing either
• NoA: UACR \<30mg/g creatinine on a first morning urine
• MiA: UACR 30-300 mg/g creatinine on a first morning urine or
• MaA: UACR \>300 mg/g creatinine on a first morning urine sample
• A documented negative serum pregnancy test for females with child bearing potential or greater than 10 years of age within (prior to) 7 days of starting the study medication.
• Subjects with child-bearing potential must be willing to use a medically accepted form of contraception throughout the study.
• Patients on hydroxyurea (HU) who are on a stable (not changing) dose of HU for three months prior to study entry.

You may not qualify if:

• Patients with Hb SC, SD, Sβ+thal, SE and other sickle hemoglobinopathies, and sickle trait (AS).
• Pregnant or lactating females, or females of child-bearing potential that are unable to use a medically accepted form of contraception throughout the study.
• Urine creatinine clearance (Clcr) \<60 mL/minute/1.73 m2
• Gross (not microscopic) hematuria. If hematuria has resolved for 2 weeks or more, patients will be eligible.
• Hyperkalemia (K≥5.5) at baseline despite a low potassium diet
• Concurrent condition that predisposes to nephropathy, such as lupus, diabetes, and hypertension, not controlled with medications..
• On a renin-angiotensin pathway inhibitor (e.g., captopril, lisinopril, Losartan, valsartan, etc) for the last two weeks prior to enrollment.
• Hypersensitivity to Angiotensin II receptor blockers such as losartan, valsartan, telmisartan.
• Patients on red cell apheresis or ongoing aggressive chronic transfusions (one or more a month with a goal of HbS \< 30%). Patients receiving a simple transfusion for symptoms during acute event will be eligible, but if they receive a partial or full exchange transfusion during an acute event, then they will only be eligible after 90 days.
• Hepatic dysfunction defined as ALT (alanine aminotransferase) or direct bilirubin \> 3-times upper limit of normal (ULN).
• Chronic therapy with NSAIDS or Cox2 inhibitors
• On another interventional trial. May be eligible two weeks after completion of another interventional study.
• Any condition that interferes with the ability of the patient to understand or comply with the treatment plan and follow up.
• A serious mental or physical illness or a major disease (cardiac, renal, hepatic, neurological, endocrine, metabolic, pulmonary function or psychiatric), which in the opinion of the investigator would compromise participation in the study.
• Unable to take oral medications.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (9)

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

University of Louisville

Louisville, Kentucky, 40201, United States

Location

NHLBI

Bethesda, Maryland, 20892, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Quinn CT, Saraf SL, Gordeuk VR, Fitzhugh CD, Creary SE, Bodas P, George A, Raj AB, Nero AC, Terrell CE, McCord L, Lane A, Ackerman HC, Yang Y, Niss O, Taylor MD, Devarajan P, Malik P. Losartan for the nephropathy of sickle cell anemia: A phase-2, multicenter trial. Am J Hematol. 2017 Sep;92(9):E520-E528. doi: 10.1002/ajh.24810. Epub 2017 Jul 19.

  PMID: 28589652 RESULT

MeSH Terms

Conditions

Kidney Diseases; Anemia, Sickle Cell

Interventions

Losartan

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Limitations and Caveats

We cannot conclude from this small phase 2 study that losartan is efficacious for sickle cell nephropathy. Rather, the data generated from this study will inform the design of a phase-3 randomized trial to determine its efficacy.

Results Point of Contact

• Title: Dr. Charles Quinn
• Organization: Cincinnati Children's Hospital Medical Center

charles.quinn@cchmc.org

5138033086

Study Officials

• Punam Malik, M.D.

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2011
• First Posted: November 24, 2011
• Study Start: February 1, 2012
• Primary Completion: November 1, 2015
• Study Completion: December 1, 2015
• Last Updated: September 29, 2020
• Results First Posted: September 29, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)