Telmisartan Versus Losartan in Kidney Transplantation

NCT01224860 | Completed Phase 2

• 2 other identifiers: COSTANT2008-000822-38
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

In renal transplant recipients, residual renal insufficiency combined to the effects of immunosuppressive therapy with steroids or calcineurin inhibitors may reduce insulin activity and may contribute to several of the abnormalities associated with the metabolic syndrome, such as hypertension, glucose intolerance and hyperlipidemia. In turn, insulin resistance, hypertension, hyperglycemia and dyslipidemia may importantly contribute to the excess cardiovascular risk of renal transplant patients (an excess comparable to that of diabetes subjects with over diabetic nephropathy)and may also accelerate progressive renal function deterioration and promote graft loss. Thus, amelioration of the insulin activity and of the related metabolic syndrome is a key component of treatments aimed to improve patient and graft survival in renal transplant recipients. Recently, drugs such as peroxisome proliferators-activated receptor-gamma activators, that ameliorate insulin sensitivity and metabolic syndrome, have become available.These agents, however, can provoke fluid retention, weight gain, edema and, in some cases, heart failure. Recent studies showed that telmisartan, an angiotensin II type 1 receptor antagonist, in addition to block the angiotensin II type 1 - a key surface receptor involved in the regulation of blood pressure - may also activate peroxisome proliferators-activated receptor-gamma activators, thus improving some of the features of the metabolic syndrome. Thus telmisartan may substantially reduce the overall cardiovascular and renal risk of renal transplant recipients by ameliorating some of the modifiable components of the metabolic syndrome. On the other hand, telmisartan is devoid of the adverse effects of peroxisome proliferators-activated receptor-gamma activators such as fluid retention, and has therefore a remarkably better risk/benefit profile. Thus, whether telmisartan in addition to the beneficial effects of a reference angiotensin II type 1 receptor antagonist (such as losartan) may offer adjunctive advantages related to improved insulin sensitivity in renal transplant patients on chronic therapy with steroids and/or calcineurin inhibitors, is worth investigating.

Conditions

Renal Transplant

Keywords

Telmisartan; Losartan; Renal transplant

Outcome Measures

Primary Outcomes (2)

• Insulin sensitivity.

  Glucose disposal rate as assessed by an euglycemic hyperinsulinemic clamp.

  At baseline and then every four months.

• Insulin sensitivity.

  Glucose disposal rate as assessed by an euglycemic hyperinsulinemic clamp.

  At 9 month.

Secondary Outcomes (6)

• Systemic variables.

  At baseline and then every four months.

• Systemic variables.

  At 9 month.

• Metabolic variables.

  At baseline and then every four months.

• Metabolic variables.

  At 9 month.

• Renal variables.

  At baseline and then every four months.

Study Arms (2)

Telmisartan

EXPERIMENTAL

Drug: Telmisartan

Losartan

EXPERIMENTAL

Drug: Losartan

Interventions

Telmisartan DRUG

One week 40 mg daily, followed by fifteen weeks treatment period with 80 mg daily.

Telmisartan

Losartan DRUG

One week 50 mg daily, followed by fifteen weeks treatment period with 100 mg daily.

Losartan

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent;
• Age \> 18 years;
• Single renal transplant or dual marginal \> 6 months duration;
• Blood pressure \>130/85 mmHg or need for anti-hypertensive therapy;
• Stable renal function (changes in serum creatinine \< 30%) and no acute rejection episodes in the last six months;
• Stable (for at least six months) dual or triple immunosuppressive therapy including corticosteroids or calcineurin inhibitors;
• Legal capacity.

You may not qualify if:

• Vascular disease of the kidney;
• Heart failure: NYHA classification class III-IV on ACE or AII inhibitor therapy;
• Cerebral haemorrhage, stroke or TIA within three months prior to study enrolment;
• Myocardial infarction within three months prior to study enrolment;
• Unstable angina pectoris;
• Severe hepatic disease;
• Pregnancy or women of child-bearing potential without following a scientifically accepted form of contraception;
• Overt diabetes or concomitant treatment with oral antidiabetic agents and/or insulin;
• Specific clinical indication (other than arterial hypertension) to be treated with ACE inhibitors or AII receptor antagonists;
• Specific contraindications or history of hypersensitivity to the study drugs, glitazones, ACE inhibitors or AII receptor antagonists;
• Participation to other clinical trials over the last three months;
• Legal incapacity;
• Previous diagnosis of: intellectual disability/mental retardation, dementia, schizophrenia.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (1)

Mario negri Institute - Clinical Research Center for Rare Diseases

Ranica, Bergamo, 24020, Italy

Location

Related Publications (1)

• 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.

  PMID: 39082471 DERIVED

MeSH Terms

Interventions

Telmisartan; Losartan

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Tetrazoles

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2010
• First Posted: October 20, 2010
• Study Start: January 1, 2009
• Primary Completion: June 1, 2013
• Study Completion: January 1, 2014
• Last Updated: February 25, 2014

Record last verified: 2014-02

Locations

IT (1)