Cardiorenal Effecs of Losartan in Kidney Transplant Recipients

• Conditions: Renal Transplant Failure; Cardiovascular Complication
• Interventions: Drug: Losartan

• Registration Number: NCT05243446
• Lead Sponsor: Medical University of Gdansk

Brief Summary

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

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 Timeline

• Study Start: 2015-09
• Study First Submitted: 2022-01-24
• Status Verified: 2022-02
• Study First Submitted QC: 2022-02-03
• Last Update Submitted: 2022-02-03
• Study First Posted: 2022-02-17
• Last Update Posted: 2022-02-17
• Primary Completion: 2022-12-31
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 740

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Study group	Losartan	Hypotensive treatment including Losartan

Primary Outcome Measures

Name	Time	Method
Occurrence of composite primary endpoint:	Up to 5 years	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.

Secondary Outcome Measures

Name	Time	Method
Urine albumine concentration	after 6 months	Difference in albuminuria in the measurements available for each patient
N-acetyl-β-D-glucosaminidase (NAG) urine excretion	after 6 months	Difference in urine NAF in the measurements available for each patient
15-F2t-isoprostanes (isoprostanes) urine excretion	after 6 months	differences in 15-F2t-isoprostanes (isoprostanes) urine excretion in the measurements available for each patient
Occurrence of cardiovascular complications	Up to 5 years	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
Decline in estimated glomerular filtration rate (eGFR)	Up to 5 years	Difference in degree of eGFR reduction
Occurrence of renal complications	Up to 5 years	ESRD or doubling of baseline serum creatinine

Trial Locations

Locations (1)

Medical University; 🇵🇱 Gdansk, Poland