Cardiorenal Effecs of Losartan in Kidney Transplant Recipients (CELART)

The influence of Losartan to cardiovascular and renal outcomes in patients after renal transplatation.

Study Overview

• Status: Recruiting
• Conditions: Renal Transplant Failure; Cardiovascular Complication
• Intervention / Treatment: Drug: Losartan

Detailed Description

The benefits of cardio and nephroprotective properties of treatment with drugs blocking the renin angiotensin aldosterone system in the general population has already been shown. There are no data on the cardiac and renal effects of this type of treatment in patients after renal transplantation.

Therefore, the observational, case-control study was designed in a population of kidney transplant recipients.

The study group consists of patients treated with antihypertensive drugs including Losartan at a minimum dose of 50mg.

The control group consists of patients treated with antihypertensive drugs, without the renin angiotensin aldosterone system blockade.

Blood pressure will be controlled in accordance with the current recommendations.

The primary aim of this study is to determine whether, in renal transplant recipients with hypertension, losartan, angiotensin II receptor antagonist improves cardiovascular and graft outcome i.e. reduces incidence of cardiovascular complications and slows progression of graft insufficiency. Secondary objective is to determine whether losartan 1. delays the occurrence of cardiovascular complications, 2. slows progression of graft insufficiency, 3. is the safe drug in renal transplant recipients, 4. decrease albuminuria and other surrogate markers of graft injury or cardiovascular involvement.

• Study Type: Observational
• Enrollment (Anticipated): 740

Contacts and Locations

• Study Contact: Name: Leszek Tylicki, professor; Phone Number: 48583492505
• Study Contact Backup: Name: Zbigniew Heleniak; Phone Number: 48583492505; Email: zth1@gumed.edu.pl

Study Locations

• Poland
  • Gdansk, Poland, 80-952
    • Recruiting
    • Medical University
    • Contact: Zbigniew Heleniak; Phone Number: 48583492505; Email: zth1@gumed.edu.pl
    • Contact: Leszek Tylicki, professor; Phone Number: 48583492505; Email: leszek.tylicki@gumed.edu.pl
    • Principal Investigator: Leszek Tylicki, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients after renal transplantation.

Description

Inclusion Criteria:

740 patients, either sex, either non-diabetic or diabetic who underwent the kidney transplantation and who:

1. Are at least three months post-transplantation
2. Have hypertension.
3. Have an estimated glomerular filtration rate greater than or equal to 30 ml/min/1.73 m2

Exclusion Criteria:

1. Pregnant or the possibility of becoming so and breast feeding.
2. Angioedema from an Angiotensin Converting Enzyme (ACE) inhibitor or Angiotensin Receptor Blocker (ARB) in the history.
3. Serum potassium greater than 5.5 mmol/l on two or more occasions in the preceding three months.
4. Graft artery stenosis (i.e. psv of more than 200 cm/s in doppler usg)
5. Left ventricular dysfunction that requires an ACE inhibitor or an ARB
6. New immunosuppressive agent was started or previous immunosuppressant stopped in the three months prior to study entry or plan to switch immunosuppressive agents within next three months.
7. Currently on four or more blood pressure pills and have an average blood pressure over three visits greater than 150/100.
8. Currently on an ACE-inhibitor or an ARB or treatment with an ACE inhibitor or ARB after kidney transplantation lasted more than 3 months.
9. Had an acute coronary syndrome, episode of malignant hypertension, stroke or transient ischaemic attack in the three months prior to study entry.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study group; Hypotensive treatment including Losartan	Drug: Losartan; losartan treatment; Other Names: Lozap, Lorista, Xartan, Losacor
Control group; Hypotensive treatment without renin-angiotensin-aldosteron system blockers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of composite primary endpoint:	Cardiovascular (CV) death and Resuscitated sudden death and Non-fatal myocardial infarction (MI) and Non-fatal stroke and Unplanned hospitalization for heart failure or unstable angina and Onset of end-stage renal disease (ESRD) and Doubling of baseline serum creatinine concentration, sustained for at least one month.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of cardiovascular complications	Cardiovascular (CV) death and Resuscitated sudden death and Non-fatal myocardial infarction (MI) and Non-fatal stroke and Unplanned hospitalization for heart failure or unstable angina	Up to 5 years
Occurrence of renal complications	ESRD or doubling of baseline serum creatinine	Up to 5 years
Decline in estimated glomerular filtration rate (eGFR)	Difference in degree of eGFR reduction	Up to 5 years
Urine albumine concentration	Difference in albuminuria in the measurements available for each patient	after 6 months
N-acetyl-β-D-glucosaminidase (NAG) urine excretion	Difference in urine NAF in the measurements available for each patient	after 6 months
15-F2t-isoprostanes (isoprostanes) urine excretion	differences in 15-F2t-isoprostanes (isoprostanes) urine excretion in the measurements available for each patient	after 6 months

Collaborators and Investigators

• Sponsor: Medical University of Gdansk
• Collaborators: Jagiellonian University; Medical University of Silesia; Pomeranian Medical University Szczecin; Nicolaus Copernicus University; Medical University of Warsaw; Wroclaw Medical University; Medical University of Bialystok; Poznan Regional Hospital
• Investigators: Principal Investigator: Leszek Tylicki, professor, Medical University of Gdansk

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: January 24, 2022
• First Submitted That Met QC Criteria: February 3, 2022
• First Posted (Actual): February 17, 2022

Study Record Updates

• Last Update Posted (Actual): February 17, 2022
• Last Update Submitted That Met QC Criteria: February 3, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: cardiovascular disease; kidney transplant recipients; angiotensin receptor blocker; albuminuria; nephroprotection
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan
• Other Study ID Numbers: ST-4/CELART

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED