Influence of Aliskiren on Albuminuria After Kidney Transplantation

Albuminuria Clinical Trial

Official title:

Influence of Aliskiren on Albuminuria After Kidney Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02446548
• Other study ID #: ST-4/Aliskiren/KTx
• Status: Completed
• Phase: N/A
• First received: May 8, 2015
• Last updated: May 13, 2015
• Start date: March 2013
• Est. completion date: November 2014

Study information

• Verified date: May 2015
• Source: Medical University of Gdansk
• Contact: n/a
• Is FDA regulated: No
• Health authority: Poland: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The study is a randomised, double-blind, controlled 2 x 3 cross-over trial in which the renal effects of therapy with aliskiren (A), placebo (P) and losartan (L) will be compared. It consists of an 8-week run-in period, 8 weeks of active treatment with aliskiren or losartan (period 1), 8 weeks of active treatment with the alternative medication (period 2), and an 8-week placebo administration between them.

Description:

At the beginning, subjects who met the inclusion criteria will enter the 8-week run-in screening period. All hypotensive group of drugs will be allowed with exception of ACEI, ARA, DRI and mineralocorticoid receptor antagonists. The target BP will be an office trough BP of 140/90 mmHg or less. At the end of the run-in period, patients will be randomly allocated to one of the two treatment sequences: L/P/A (sequence 1) or A/P/L (sequence 2) . The study medications will be introduced as single hypotensive drug or added to the current hypotensive agents, the dosage of which, once adjusted in the run-in period, will be left unchanged throughout the study. Losartan will be used at a dose of 50 mg and aliskiren will be administered at a dose of 150 mg. Drug compliance will be assessed by tablet counts. Patients will be recommended not to change their usual daily protein and sodium intake during the study period. Dosage of cyclosporine or tacrolimus will be not allowed to change either. At the end of each of the three treatment periods, office thorough BP, 24-h ambulatory BP, albuminuria, serum creatinine and potassium, haemoglobin, cyclosporine or tacrolimus level, urine excretion of NAG, TGF-β-1 and 15-F2t-isoprostanes will be determined. eGFR will be calculated. Patients will be also asked to fill in the questionnaire for measuring patients-reported side effects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: November 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Transplantation period above 6 months,

2. Calcineurin inhibitor (cyclosporine or tacrolimus) based immunosuppression,

3. Stable cyclosporine or tacrolimus trough level in the last three months (no variations above 25%),

4. Stable renal function defined as eGFR > 30 ml/min (no variations above 5 ml/min/1.73 m2 in the last 3 months),

5. Arterial hypertension treated with one or two antihypertensive agents or blood pressure (BP) > 130/80 mmHg in patients not treated yet,

6. Albuminuria > 30 mg/g creatinine.

Exclusion Criteria:

1. Pregnant or the possibility of becoming so and breast feeding.

2. Angioedema from an ACE inhibitor or ARA 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 ARA Protocol Version 1 p. 5 of 10

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 ARAor treatment with an ACE inhibitor or ARA 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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Albuminuria

Intervention

Drug:
• aliskiren
aliskiren will be administered at a dose of 150 mg, each dose was to be taken orally with water once daily at approximately 8:00 A.M., except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed. Drug compliance will be assessed by tablet counts.
• losartan
losartan will be administered at a dose of 50 mg, each dose was to be taken orally with water once daily at approximately 8:00 A.M. except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed. Drug compliance will be assessed by tablet counts.

Other:
• Placebo
placebo will be administered once daily orally (1 tablet) in the morning with water at approximately 8:00 A.M. except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed. Compliance will be assessed by tablet counts. Placebo was prapared in Department of Pharmaceutical Technology MU Gdansk

Locations

Country	Name	City	State
Poland	Medical University of Gdansk	Gdansk	Pomorskie

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Gdansk

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	a difference in albuminuria in the measurements available for each patient		after 8 weeks of treatment	No
Secondary	a differences in N-acetyl-ß-D-glucosaminidase (NAG) urine excretion in the measurements available for each patient		after 8 weeks of treatment	No
Secondary	a differences in transforming growth factor ß-1 (TGF-ß-1) urine excretion in the measurements available for each patient		after 8 weeks of treatment	No
Secondary	a differences in 15-F2t-isoprostanes (isoprostanes) urine excretion in the measurements available for each patient		after 8 weeks of treatment	No