Rosuvastatin for Preventing Complications in Renal Ablation

NCT ID: NCT01899027

Last Updated: 2013-07-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 112 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2017-12-31

Brief Summary

The primary objective of this study is to test the hypothesis that twice overnight high-dose rosuvastatin loading before RNA followed by 3-month treatment with regular doses of rosuvastatin can reduce both the acute and late renal artery damage.

Detailed Description

Despite the availability and use of different classes of antihypertensive drugs, 5-30% of patients still show elevated blood pressure (EUROASPIRE III survey, 2011).

Recently, a novel catheter-based radiofrequency ablation technique has been developed allowing for renal nerve ablation (RNA). Currently, two different catheter-based systems are primarily used (Simplicityw catheter by Medtronic-Adrian and the EnligHTNTM multi-electrode RNA catheter from St Jude Medical).

The RNA technique has been associated with a very low complication rate, but the development of a renal artery stenosis after RNA has been reported (J Am Coll Cardiol 2012;60:2694-2695).

Although little is known about the vascular injury induced by the RNA procedure at the site of ablation, a recent study has reported for the first time the evidence at optical coherence tomography (OCT) of local vascular injury induced by the radiofrequency energy. Such local tissue damage, which is not apparent with angiography, is characterized by local and diffuse vasospasm, oedema formation, and endothelial injury with thrombus generation (Templin et al. Eur Heart J, 25 April 2012).

Experimental research have suggested that these abnormalities are only present in the acute phase immediately after RNA and seem to be the consequence of a transient phenomenon of inflammation (Clin Res Cardiol 2011;100:1095-1101), similarly to what occurs in the coronary arteries after percutaneous coronary intervention (PCI).

In the last decade, multiple studies have convincingly shown that the pre-procedural administration of statins can significantly reduce the extent of cardiac damage at time of PCI (Patti et al, JACC 2011). No previous investigation, however, has assessed whether pre-procedural statin load play any protective role on renal arteries at time of RNA.

Study Population Patients with resistant arterial hypertension scheduled to undergo renal artery ablation

Randomization Patients will be randomized to receive two overnight high doses of Rosuvastatin (40 mg 12 h before RNA and another 10 mg dose 2 h before the procedure, N=50) or placebo (N=50).

Study design Patients will be randomized to receive two overnight high doses of Rosuvastatin (40 mg 12 h before RNA and another 10 mg 2 hours prior to the procedure, N=56) or placebo (N=56).

RNA will be performed with two different catheter-based systems (Simplicityw catheter by Medtronic-Adrian and the EnligHTNTM multi-electrode RNA catheter from St Jude Medical).

All patients will have OCT utilizing the C7-XR imaging system (Light-Lab Imaging, Inc., Westford, USA) before and after renal denervation of both renal arteries.

After the procedure, patients included in the Rosuvastatin-group will be given rosuvastatin 10 mg/day for 3 months and patients included in the Placebo-group will receive placebo 1 pill/day for 3 months.

At end of the 3-month follow-up period, patients will undergo repeat OCT of both renal arteries.

Sample size If we expect an incidence of 50% for each of the three primary endpoints (vasospasm, oedema or thrombus) in the control arm and hypothesize a 50% risk reduction of such incidence in the rosuvastatin arm, a total sample size of 112 patients would provide 80% power to detect this difference with an alpha level of 0.05.

Duration of the trial: 1 year

Primary End-point

Optical coherence tomography evidence of vascular injury induced by the radiofrequency energy, as detected by the evidence of at least one of the following 3 abnormalities:

• Presence (vs. absence) of local and diffuse vasospasm (i.e. as defined by immediate loss of lumen area or lumen diameter in any part of renal artery)
• Presence (vs.r absence) of oedema formation (i.e. as defined as any significant endothelial-intimal notch detected on the luminal wall surface)
• Presence (vs. absence) of endothelial injury (i.e. disruptions of the superficial intimal lining defined as endothelial detachments or vessel dissections) with thrombus generation (i.e. as a protruding mass attached to the luminal surface with a diameter of 0.5 mm in at least three following cross-sections)

Secondary End-points

• Comparison of the extent of vascular injury between the two catheter-based systems used for the study (EnligHTNTM vs. Simplicityw)
• Comparison vs. baseline of 24-hour and 48-hour post-procedural changes in CRP, creatinine. eGFR (as expressed in ml/min/1.73 m2), urine albumin:creatinine ratio, and absolute values of NGAL (Neutrophil gelatinase-associated lipocalin).

Expected findings According to a previous preliminary experience with optical coherence tomography (Templin et al. Eur Heart J, 25 April 2012), the expected frequency of vascular injury in statin-naïve patients is 42% for vasospasm, 96% for oedema, and 67% for thrombus.

We expect a reduction of at least 25% in the frequency of abnormalities with pre-treatment with rosuvastatin.

Conditions

Arterial Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Rosuvastatin Group

Patients will be randomized to receive two overnight high doses of Rosuvastatin (40 mg 12 h before RNA and another 10 mg dose 2 h before the procedure

Group Type: ACTIVE_COMPARATOR

Rosuvastatin

Intervention Type: DRUG

Patients will receive two overnight high doses of Rosuvastatin (40 mg 12 h before RNA and another 10 mg dose 2 h before the procedure

Placebo group

Patients will be randomized to receive two overnight high doses of Placebo before RNA and another placebo dose 2 h before the procedure

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Patients will receive two overnight doses of Placebo 12 h before RNA and another dose 2 h before the procedure

Interventions

Rosuvastatin

Patients will receive two overnight high doses of Rosuvastatin (40 mg 12 h before RNA and another 10 mg dose 2 h before the procedure

Intervention Type: DRUG

Placebo

Patients will receive two overnight doses of Placebo 12 h before RNA and another dose 2 h before the procedure

Intervention Type: DRUG

Other Intervention Names

Crestor® (rosuvastatin calcium)

Eligibility Criteria

Inclusion Criteria

• Primary and idiopathic cause of resistant arterial hypertension defined as persistent systolic blood pressure persistent systolic blood pressure - 160 mm Hg, with at least established three antihypertensive medication (including diuretics)
• Patients with allergies to antihypertensive drugs
• Able to understand and willing to sign the informed CF

Exclusion Criteria

• Glomerular filtration rate <45 mL/min
• LDL Cholesterol >130 mg/dl
• Presence of coronary artery disease
• History of myopathy or elevated creatine kinase levels
• History of Impaired liver function and/or elevated ALT and/or AST levels
• Women of child bearing potential patients must demonstrate a negative pregnancy test performed within 24 hours before CT

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Roma La Sapienza

OTHER

Sponsor Role: lead

Responsible Party

Francesco Pelliccia

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cesare Greco, MD

Role: STUDY_DIRECTOR

University Sapienza

Locations

University Sapienza

Rome, , Italy

Countries

Italy

Central Contacts

Cesare Greco, MD

Role: CONTACT

cesare.greco@uniroma1.it

+390649971 ext. 123

Francesco Pelliccia, MD

Role: CONTACT

f.pelliccia@mclink.it

+390649971 ext. 123

Facility Contacts

Cesare Greco, MD

Role: primary

cesare.greco@uniroma1.it

+390649971 ext. 123

Francesco Pelliccia, MD

Role: backup

f.pelliccia@mclink.it

+390649971 ext. 123

Other Identifiers

553/2013/D

Identifier Type: -

Identifier Source: org_study_id