Influence of Aliskiren on Albuminuria After Kidney Transplantation

NCT ID: NCT02446548

Last Updated: 2015-05-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2014-11-30

Brief 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.

Detailed 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.

Conditions

Albuminuria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

aliskiren - placebo - losartan

aliskiren (Rasilez) 150 mg; losartan (Xartan) 50 mg

Group Type: EXPERIMENTAL

aliskiren

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Placebo

Intervention Type: OTHER

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 Gdańsk

losartan - placebo - aliskiren

aliskiren (Rasilez) 150 mg; losartan (Xartan) 50 mg

Group Type: EXPERIMENTAL

aliskiren

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Placebo

Intervention Type: OTHER

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 Gdańsk

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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 Gdańsk

Intervention Type: OTHER

Other Intervention Names

Rasilez (Novarits Europe); Xartan (Adamed, Poland)

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of Gdansk

OTHER

Sponsor Role: lead

Responsible Party

Leszek Tylicki

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Boleslaw Rutkowski, Prof.

Role: PRINCIPAL_INVESTIGATOR

Deaprtment of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk

Locations

Medical University of Gdansk

Gdansk, Pomeranian Voivodeship, Poland

Countries

Poland

References

Natale P, Mooi PK, Palmer SC, Cross NB, Cooper TE, Webster AC, Masson P, Craig JC, Strippoli GF. Antihypertensive treatment for kidney transplant recipients. Cochrane Database Syst Rev. 2024 Jul 31;7(7):CD003598. doi: 10.1002/14651858.CD003598.pub3.

Reference Type: DERIVED

PMID: 39082471 (View on PubMed)

Other Identifiers

ST-4/Aliskiren/KTx

Identifier Type: -

Identifier Source: org_study_id