Preventing Sickle Cell Kidney Disease

NCT02373241 | Terminated Phase 2 Results DMC

• 2 other identifiers: F1411070091K23HL127100-01
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Untreated hypertension and renal injury are risk factors for increased morbidity and mortality in sickle cell disease, yet early markers of progressive disease have not been identified and therapies to prevent the development of adverse cardiovascular outcomes have not been defined. Circadian blood pressure, as defined by 24 hour blood pressure monitoring, is more accurate than clinic blood pressure in defining secondary hypertension and abnormal nocturnal blood pressured dipping and nocturnal hypertension have been linked to progressive renal disease in other diseases. Methodology/Aims: A randomized feasibility trial of losartan will be conducted among adolescent HbSS and SB0 thalassemia patients (11-19 years) with abnormal nocturnal blood pressure dipping. During this six month feasibility trial, two dosing strategies of losartan (titrated to keep clinic BP \<95th percentile vs. \<75th percentile) will be analyzed for safety and effect on restoring normal circadian blood pressure. A prospective cohort study among HbSS and SB0 thalassemia patients (6-19 years) will also be conducted to evaluate the incidence of hypertension and role of monitoring potential biomarkers of kidney injury and hypertension. Cohort participants will undergo annual evaluations of hypertension(24 hour blood pressure monitoring for participants ≥ 11yrs, clinic BP in all participants) and markers of kidney injury/hypertension. Expected Results: At the completion of the feasibility trial, vital background information will be obtained to design a definitive multicenter trial of hypertension in sickle cell disease. At the completion of the cohort study, the incidence of pediatric hypertension will be identified and the role for monitoring blood and urine biomarkers will be better understood. As therapy for patients with renal failure is dismal, it is imperative that SCD patients at risk are identified early and that therapeutic trials are conducted that prevent progression.

Conditions

Anemia, Sickle Cell; Sickle Cell Disease; Kidney Disease; Hypertension; Proteinuria

Keywords

Anemia, Sickle Cell; Sickle Cell Disease; Kidney Disease; Hypertension; Proteinuria; Losartan; Antihypertensive Agents; Blood Pressure

Outcome Measures

Primary Outcomes (1)

• Feasibility as Measured by the Number of Patients That Accept Enrollment, Remain Adherent to Losartan, and Remain Adherent to Study Procedures.

  Outcome 1a. Document the rate of acceptance (quantitative) and reasons for acceptance/rejection (qualitative) in a randomized trial of trial of losartan for SCD patients with abnormal nocturnal blood pressures. Outcome 1b. Identify the adherence rate to losartan during a randomized three year trial of losartan for SCD patients (n=40) with abnormal nocturnal blood pressure. Outcome 1c. Determine the adherence rate to study procedures among participants enrolled in a three year trial of losartan for SCD patients (n=40) with abnormal nocturnal blood pressure.

  5 yrs

Secondary Outcomes (2)

• Number of Patients With Incident Hypertension

  5 yrs

• Feasibility as Measured by the Number of Patients With Improvement in Nocturnal Blood Pressure While Receiving Losartan.

  5 years

Study Arms (2)

Standard Blood Pressure Management

ACTIVE COMPARATOR

Participants initiated on 25mg of losartan daily and randomized to lower in-clinic BP to \<95th percentile

Drug: Losartan

Experimental Blood Pressure Management

EXPERIMENTAL

Participants initiated on 25mg of losartan daily and randomized to lower in-clinic BP to \<75th percentile

Drug: Losartan

Interventions

Losartan DRUG

Standard dosing

Also known as: coozar

Standard Blood Pressure Management

Eligibility Criteria

• Age: 5 Years - 25 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Pts with HbSS or SB0 thalassemia
• Hypertension from clinic BP readings (defined by NHLBI BP tables)
• Abnormal nocturnal dipping (systolic or diastolic) as defined by \<10% dip or abnormal nocturnal BP load (\>25% of sleep BP readings \>95th percentile as defined by AHA ABPM guidelines)
• Signed Informed Consent

You may not qualify if:

• Patient already on BP lowering medication
• Hyperkalemia
• Pregnancy

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35223, United States

Location

Related Publications (9)

• Samuels J, Ng D, Flynn JT, Mitsnefes M, Poffenbarger T, Warady BA, Furth S; Chronic Kidney Disease in Children Study Group. Ambulatory blood pressure patterns in children with chronic kidney disease. Hypertension. 2012 Jul;60(1):43-50. doi: 10.1161/HYPERTENSIONAHA.111.189266. Epub 2012 May 14.

  PMID: 22585950 BACKGROUND

• Seeman T, Palyzova D, Dusek J, Janda J. Reduced nocturnal blood pressure dip and sustained nighttime hypertension are specific markers of secondary hypertension. J Pediatr. 2005 Sep;147(3):366-71. doi: 10.1016/j.jpeds.2005.04.042.

  PMID: 16182677 BACKGROUND

• Okuguchi T, Osanai T, Fujiwara N, Kato T, Metoki N, Konta Y, Okumura K. Effect of losartan on nocturnal blood pressure in patients with stroke: comparison with angiotensin converting enzyme inhibitor. Am J Hypertens. 2002 Nov;15(11):998-1002. doi: 10.1016/s0895-7061(02)02998-9.

  PMID: 12441222 BACKGROUND

• Flynn JT, Daniels SR, Hayman LL, Maahs DM, McCrindle BW, Mitsnefes M, Zachariah JP, Urbina EM; American Heart Association Atherosclerosis, Hypertension and Obesity in Youth Committee of the Council on Cardiovascular Disease in the Young. Update: ambulatory blood pressure monitoring in children and adolescents: a scientific statement from the American Heart Association. Hypertension. 2014 May;63(5):1116-35. doi: 10.1161/HYP.0000000000000007. Epub 2014 Mar 3. No abstract available.

  PMID: 24591341 BACKGROUND

• Lebensburger JD, Palabindela P, Howard TH, Feig DI, Aban I, Askenazi DJ. Prevalence of acute kidney injury during pediatric admissions for acute chest syndrome. Pediatr Nephrol. 2016 Aug;31(8):1363-8. doi: 10.1007/s00467-016-3370-0. Epub 2016 Mar 24.

  PMID: 27011218 BACKGROUND

• Aban I, Baddam S, Hilliard LM, Howard TH, Feig DI, Lebensburger JD. Severe anemia early in life as a risk factor for sickle-cell kidney disease. Blood. 2017 Jan 19;129(3):385-387. doi: 10.1182/blood-2016-09-738104. Epub 2016 Dec 5. No abstract available.

  PMID: 27919909 BACKGROUND

• Baddam S, Aban I, Hilliard L, Howard T, Askenazi D, Lebensburger JD. Acute kidney injury during a pediatric sickle cell vaso-occlusive pain crisis. Pediatr Nephrol. 2017 Aug;32(8):1451-1456. doi: 10.1007/s00467-017-3623-6. Epub 2017 Feb 25.

  PMID: 28238158 BACKGROUND

• Lebensburger JD, Cutter GR, Howard TH, Muntner P, Feig DI. Evaluating risk factors for chronic kidney disease in pediatric patients with sickle cell anemia. Pediatr Nephrol. 2017 Sep;32(9):1565-1573. doi: 10.1007/s00467-017-3658-8. Epub 2017 Apr 5.

  PMID: 28382567 BACKGROUND

• Lebensburger JD, Aban I, Hilliard LM, Feig DI. Hyperuricemia and abnormal nocturnal dipping impact glomerular filtration rate in patients with sickle cell anemia. Am J Hematol. 2021 May 1;96(5):E143-E146. doi: 10.1002/ajh.26115. Epub 2021 Feb 18. No abstract available.

  PMID: 33524174 BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell; Kidney Diseases; Hypertension; Proteinuria

Interventions

Losartan

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Jeffrey Lebensbugrer
• Organization: University of Alabama at Birmingham

jlebensburger@uabmc.edu

2056389285

Study Officials

• Jeffrey D Lebensburger, DO, MSPH

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatric Hematology Oncology

Study Record Dates

• First Submitted: February 5, 2015
• First Posted: February 26, 2015
• Study Start: April 1, 2015
• Primary Completion: February 1, 2021
• Study Completion: July 1, 2021
• Last Updated: April 3, 2024
• Results First Posted: May 9, 2022

Record last verified: 2024-04

Locations

US (1)