Kilt Technique as an Angle Modification Method for Endovascular Repair of Abdominal Aortic Aneurysm with Severe Neck Angle.

PURPOSE: Kilt technique can be useful for overcoming the severe angle in endovascular abdominal aortic repair. Thus, we investigate the utility of the Kilt technique as an angle modification method. METHODS: This study included 16 patients with abdominal aortic aneurysm having severe neck angle (over 60°). Of these, eight were treated using Kilt technique, whereas the remaining eight were by the conventional endovascular method. We investigated the pre- and post-procedural differences in neck angle between the two groups using aortic computed tomography (CT) angiography. RESULTS: Mean pre-procedural neck angles in the conventional group and the Kilt group were 70° ± 13° and 93° ± 14° (p = 0.007) and supra-renal neck angles were 54° ± 16° and 89° ± 26°, respectively (p = 0.016). However, the angle differences disappeared between the two groups after the procedure. Consequently, the Kilt group showed greater angle change than the conventional group (p value for ∆ supra-renal angle and ∆ neck angle were 0.015 and 0.021, respectively). There was no type 1 endoleak during 16 ± 16 months of CT follow-up. CONCLUSION: Kilt technique may be an effective tool for modifying the neck angle without leaving increased risk of type 1 endoleak in this subset of patients.

First-Generation Versus Second-Generation Drug-Eluting Stents in Coronary Chronic Total Occlusions: Two-Year Results of a Multicenter Registry.

BACKGROUND: Limited data are available regarding the long-term clinical outcomes of second-generation drug-eluting stents (DES) versus first-generation DES in patients with coronary chronic total occlusion (CTO) who undergo percutaneous coronary intervention (PCI). The aim of this study was to compare the clinical outcomes of second-generation DES with those of first-generation DES for the treatment of CTO. METHODS AND RESULTS: Between March 2003 and February 2012, 1,006 consecutive patients with CTO who underwent successful PCI using either first-generation DES (n = 557) or second-generation DES (n = 449) were enrolled in a multicenter, observational registry. Propensity-score matching was also performed. The primary outcome was cardiac death over a 2-year follow-up period. No significant differences were observed between the two groups regarding the incidence of cardiac death (first-generation DES versus second-generation DES; 2.5% vs 2.0%; hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.37 to 1.98; p = 0.72) or major adverse cardiac events (MACE, 11.8% vs 11.4%; HR: 1.00; 95% CI: 0.67 to 1.50; p = 0.99). After propensity score matching, the incidences of cardiac death (HR: 0.86; 95% CI: 0.35 to 2.06; p = 0.86) and MACE (HR: 0.93; 95% CI: 0.63 to 1.37; p = 0.71) were still similar in both groups. Furthermore, no significant differences were observed between sirolimus-eluting, paclitaxel-eluting, zotarolimus-eluting, and everolimus-eluting stents regarding the incidence of cardiac death or MACE. CONCLUSION: This study shows that the efficacy of second-generation DES is comparable to that of first-generation DES for treatment of CTO over 2 years of follow-up.

Numbness after Transradial Cardiac Catheterization: the Results from a Nerve Conduction Study of the Superficial Radial Nerve.

BACKGROUND AND OBJECTIVES: Numbness on the hand occurs infrequently after a transradial cardiac catheterization (TRC). The symptom resembles that of neuropathy. We, therefore, investigated the prevalence, the predicting factors and the presence of neurological abnormalities of numbness, using a nerve conduction study (NCS). SUBJECTS AND METHODS: From April to December 2013, all patients who underwent a TRC were prospectively enrolled. From among these, the patients who experienced numbness on the ipsilateral hand were instructed to describe their symptoms using a visual analogue scale; subsequently, NCSs were performed on these patients. RESULTS: Of the total 479 patients in the study sample, numbness occurred in nine (1.8%) following the procedure. The NCS was performed for eight out of the nine patients, four (50%) of which had an abnormal NCS result at the superficial radial nerve. A larger sheath and history of myocardial infarction (p=0.14 and 0.08 respectively) tended towards the occurrence of numbness; however, only the use of size 7 French sheaths was an independent predictor for the occurrence of numbness (odds ratio: 5.50, 95% confidence interval: 1.06-28.58, p=0.042). The symptoms disappeared for all patients but one, within four months. CONCLUSION: A transient injury of the superficial radial nerve could be one reason for numbness after a TRC. A large sheath size was an independent predictor of numbness; therefore, large sized sheaths should be used with caution when performing a TRC.

Embolization of persistent false lumen through reentry tear in a patient who underwent hemiarch replacement operation due to type A dissection.

We used endovascular techniques to treata 67-year-old male patient who had a persistent false lumen (FL) owing to a remnant tear at the ascending aorta after a hemiarch replacement operation. Attempted insertion of a catheter into the tear site in the ascending aorta failed because of the anatomic difficulty. However, an alternative FL pathway was made to reach the opening site by entering the reentry tract. Complete thrombosis of FL with coils and vascular plug was achieved. The FL channel can be used as an alternative pathway to allow a catheter to reach the tear site of the proximal aorta.

Biodegradable polymer biolimus-eluting stent versus durable polymer everolimus-eluting stent in patients with acute myocardial infarction.

BACKGROUND: There are limited data about long-term outcomes for biodegradable polymer biolimus-eluting stent (BES) versus durable polymer everolimus-eluting stent (EES) in patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). We sought to compare the two-year efficacy and safety of BES versus EES in AMI patients. METHODS: A total of 707 consecutive patients with ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction who underwent PCI with BES (n=171) or EES (n=536) between July 2008 and June 2012 were enrolled in this study. The efficacy endpoint (target vessel failure; a composite of cardiac death, target vessel-related myocardial infarction, and target vessel revascularization) and the safety endpoint (a composite of all cause death, myocardial infarction, and stent thrombosis) at two years were compared in crude and propensity score-matched cohorts. RESULTS: After two years, target vessel failure occurred in 13 patients treated with BES and 49 patients treated with EES (7.6% versus 9.1%; adjusted hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.58-2.04; p=0.78). The rates of composite safety endpoint at two years were not different between two groups (BES 7.6% versus EES 10.8%; adjusted HR, 0.87; 95% CI, 0.47-1.62; p=0.66). The rates of stent thrombosis did not differ between two groups (BES 0.6% versus EES 1.3%; adjusted HR, 0.63; 95% CI, 0.06-6.20; p=0.69). These findings were substantiated by similar results in the propensity score-matched cohort. CONCLUSIONS: In the treatment of patients with AMI, BES showed similar efficacy and safety compared to those of EES for up to two years.

Impact of final kissing balloon inflation after simple stent implantation for the treatment of non-left main true coronary bifurcation lesions in patients with acute coronary syndrome.

OBJECTIVES: We sought to evaluate the impact of final kissing balloon inflation (FKBI) after simple stent implantation for the treatment of non-left main true coronary bifurcation lesions in patients with acute coronary syndrome (ACS). BACKGROUND: Whether FKBI should be mandatory after simple stent implantation for the treatment of coronary bifurcation lesion is controversial. Besides, ACS patients who have undergone bifurcation percutaneous coronary intervention with simple stent implantation may experience worse prognosis compared to stable angina pectoris patients. METHODS: Two hundred and fifty one eligible patients (67.7% male, mean age 61.7 ± 10.4 years) were enrolled. The study population was divided into two groups according to the performance of FKBI. The primary end points were major adverse cardiac event (MACE); target lesion revascularization (TLR), non-fatal myocardial infarction (MI) and cardiac death during the follow-up period. RESULTS: Over a mean follow-up period of 3.0 ± 1.9 years, there were 29 MACEs (10 TLR, 6 non-fatal MI, and 13 cardiac deaths), representing an event rate of 11.6%. Kaplan-Meier survival analysis revealed that FBKI group had favorable outcome compared to non-FKBI group with regard to hard events (p = 0.010) as well as composite MACEs (p = 0.008). In multivariable analysis, FKBI was a significant predictor of composite MACEs [hazard ratio 0.398 (95% confidence interval 0.190-0.836, p = 0.015)] and hard events [hazard ratio 0.325 (95% confidence interval 0.130-0.811, p = 0.016)]. CONCLUSIONS: In terms of prognosis, performing FKBI after simple stent implantation for the treatment of non-left main true coronary bifurcation lesions may be mandatory in ACS patients.

Acute ST Elevated Myocardial Injury due to Coronary Thrombosis during Thoracic Endovascular Aortic Repair in Patient with Protein S Deficiency.

A 71-year-old woman who had suffered from pulmonary thromboembolism with deep vein thrombosis for 12 years presented the hospital with a huge thoracic aortic aneurysm. During thoracic endovascular therapy, she had a sudden coronary artery occlusion without having organized stenosis or plaque rupture even under the dual antiplatelet treatment and heparinization. She turned out to be having a protein S deficiency. A procedure related thrombotic adverse event in patient with protein S deficiency is very rare, so we report a case with literature review.

Large false lumen area is a predictor of failed false lumen volume reduction after stent-graft repair in type B aortic dissection.

PURPOSE: To investigate the predictors of failed false lumen (FL) volume reduction at 12 months after stent-graft implantation in patients with type B aortic dissection. METHODS: The retrospective analysis comprised 38 patients (25 men; mean age 60±12 years) with double-barrel type B aortic dissection (9 acute) treated with thoracic endovascular aortic repair (TEVAR) and evaluated with serial computed tomography (CT) scans up to 12 months. Aortic volume changes were determined. Based on FL volume change at 1 year after stent-graft implantation, patients were dichotomized according to the presence or absence of FL volume reduction. Clinical and CT variables were compared between groups to determine risk factors of failed FL volume reduction. A major adverse event (MAE) was defined as death or reintervention. RESULTS: Patients were followed for 4.2±2.8 years. FL volume reduction (+FLVR) occurred in 27 (71%) patients, whereas 11 (29%) patients had no FL volume reduction (-FLVR). The MAE-free survival rate was significantly higher in the +FLVR patients than in the -FLVR group (88.9% vs. 27.3%, respectively; p=0.001). Chronicity of dissection, location of tear site, or the maximum total aortic lumen area was not associated with failure to achieve FL volume reduction. However, the maximum preprocedure FL area was significantly lower in the +FLVR group than in the -FLVR group (12.6±6.6 vs. 21.0±11.4 cm(2), respectively; p=0.041) and was an independent predictor for failed FL volume reduction (odds ratio 1.3, 95% confidence interval 1.02 to 1.70, p=0.031). CONCLUSION: Failed FL volume reduction after TEVAR was associated with a significantly increased rate of mortality or reintervention during follow-up. A larger preprocedure maximum FL area was a predictor of failed FL volume reduction after TEVAR in type B dissection.

Effects of combination therapy with cilostazol and probucol versus monotherapy with cilostazol on coronary plaque, lipid and biomarkers: SECURE study, a double-blind randomized controlled clinical trial.

AIM: The study aim is to investigate synergistic effects of cilostazol and probucol combination therapy on coronary plaque volume and composition. METHODS: A total of 119 patients undergoing coronary stenting were treated with probucol and cilostazol combination therapy (group Ⅰ) or with cilostazol monotherapy (group Ⅱ) in a double-blind, randomized multicenter trial, and evaluated by virtual histology intravascular ultrasound (VH-IVUS) at baseline and 9-month follow-up for changes in coronary plaque volume and composition at an index intermediate lesion with luminal narrowing ≥30% and ＜70% and for neointimal hyperplasia at the stented segment. In all patients simvastatin 20 mg was started with enrollment. RESULTS: Qualifying VH-IVUS data from 91 patients were included in the final analysis. There were no significant differences between group Ⅰ and Ⅱ with respect to the primary endpoint, nominal change in normalized total atheroma volume (TAV) of the index intermediate coronary lesion (Δ-12.6±17.7 vs. -14.2±20.2 mm(3), p=0.691), or plaque composition. Plaque regression was observed in more than 70% of patients in both groups. Diabetes was the only significant independent determinant of changes in TAV (ß=0.22, p=0.037). There were greater decreases in total cholesterol (Δ-51.8±33.0 vs. -25.4±39.1 mg/dL, p＜0.001) and LDL (Δ-33.5±30.5 vs. -20.3±30.8 mg/dL, p=0.044) levels in group Ⅰ than in group Ⅱ. However, HDL cholesterol (Δ-11.2±8.5 vs. 2.7±7.7 mg/dL, p＜0.001) and apoA1 (Δ-18.2±21.4 vs. 10.0±16.5 mg/dL, p＜0.001) levels were also significantly decreased in group Ⅰ compared with group Ⅱ. CONCLUSIONS: There were no significant differences in changes in plaque volume or composition between the cilostazol and probucol combination therapy and cilostazol monotherapy group despite different impacts of the treatments on lipid biomarkers.

Postclose technique for large sheath arterial access using perclose(TM) in emergency endovascular repair.

The "Preclose technique" using a perclose device has recently become widely used in various percutaneous procedures requiring a large access sheath. However, the post-procedural application of the perclose(TM) to the large sheath arteriotomy is more challenging because of the risk of bleeding and difficulty of device application. This report introduces a novel post-procedural closing technique of large 22 Fr arterial sheath access using perclose devices.

A comparison of clinical features of coronary artery spasm with and without thyrotoxicosis.

OBJECTIVE: Several reports have suggested that thyrotoxicosis may induce severe coronary artery spasm (CAS). However, there are few data regarding the differences in clinical characteristics of CAS with and without thyrotoxicosis. The aim of our study is to compare the clinical features of CAS with and without thyrotoxicosis. METHODS: We evaluated 430 consecutive patients with CAS [patients with thyrotoxicosis (N=32, group I) and those without (N=398, group II)] at a single institute between January 2001 and June 2011. We compared clinical presentations, angiographic findings, and adverse outcomes (a composite outcome of cardiac death, myocardial infarction, or rehospitalization due to cardiac cause) of both groups. RESULTS: There was higher incidence of acute myocardial infarction at initial presentation in group I (15.6 vs. 5.8%, P=0.04). CAS with thyrotoxicosis was more diffuse (59.4 vs. 39.3%, P=0.03), more medically intractable (9.4 vs. 0%, P=0.001), and more frequently involved the left main vessel (25.0 vs.0.8%, P=0.001) than CAS without thyrotoxicosis. During the follow-up period (median 43 months), there were no significant differences between the two groups in terms of the risk of adverse outcomes (hazard ratio for CAS with thyrotoxicosis, 1.029; 95% confidence interval, 0.347-3.054). CONCLUSION: Clinical and angiographic presentations of CAS with thyrotoxicosis were more severe than CAS without thyrotoxicosis, but clinical outcomes were similar in both groups. Optimal vasodilator therapy is essential for the management of CAS with thyrotoxicosis. Thyroid function test should be mandatory for all patients with CAS.

A case of successful bare metal stenting for aortic coarctation in an adult.

Aortic coarctation is a correctable hypertensive disease. For safety reasons and due to the invasiveness of surgical techniques, percutaneous interventions have become drastically more popular in recent times. In elderly patients with aortic coarctation who are at risk of an aortic wall aneurysm and rupture, covered stents are preferred but in younger patients, bare metal stenting may be sufficient for long-term safety. Herein we present a 47-year-old typical aortic coarctation patient who was successfully treated with a bare metal stent.

Hybrid endovascular repair for aortic arch pathology: intermediate outcomes and complications: a retrospective analysis.

OBJECTIVES: To evaluate the outcomes of hybrid endovascular repair for aortic arch pathology. METHODS: This study was a retrospective analysis involving patients who underwent hybrid endovascular repair for aortic arch pathologies. RESULTS: Twenty-one patients (16 men; mean age, 64.7 ± 16.2 years) with aortic arch pathologies were treated by hybrid endovascular repair. The indications for treatment included increased aneurysm size in 16 cases (71.4%), rupture or impending aneurysmal rupture in 5 cases (23.8%), and rapid growth of aortic dissection (≥ 10 mm/y) in 1 case (4.8%). Supra-aortic vessel transposition and stent-graft implantation were achieved in all cases. Two types of stent-graft was used, as follows: the Seal thoracic stent-graft in 14 patients (66.7%); and the Valiant stent grafts in 7 patients (33.3%). Perioperative complications affected 5 patients (23.8%), as follows: bleeding (n = 4, 19.0%); stroke (n = 3, 14.3%); renal failure (n = 2, 9.5%); vascular injury (n = 1, 4.8%), and respiratory failure (n = 1, 4.8%). Two patients died within 30 days (9.5%). Technical success was achieved in 15 patients (71.5%). Early endoleaks were noted in 4 patients (19.0%). One patient died during follow-up (mean, 21.3 ± 11.6 months) due to a de novo intramural hematoma. Persistent early endoleaks were noted in 4 patients (19.0%); 2 of the 4 patients were successfully managed with implantation of additional stent-grafts. No late onset endoleaks were noted. The death-free survival and reintervention-free survival rates during follow-up were 85.7% and 90.5%, respectively. CONCLUSION: Hybrid treatment with supra-aortic vessel transposition and endovascular repair may be an option in frail patients in who open procedures is too risky.

Percutaneous cardiopulmonary support-supported percutaneous coronary intervention: a single center experience.

BACKGROUND AND OBJECTIVES: Percutaneous cardiopulmonary support (PCPS) has proven to be a valuable technique in high-risk coronary patients undergoing percutaneous coronary intervention (PCI). However, there have been few studies on PCI associated with PCPS in Korea. We summarized our experience with PCPS-supported PCI. SUBJECTS AND METHODS: We retrospectively reviewed 19 patients with PCPS-supported PCI between August 2005 and June 2009. PCPS was used as an elective procedure for 10 patients with at least two of the following conditions: left-ventricular ejection fraction <35%, target vessel(s) supplying more than 50% of the viable myocardium, high risk surgical patients, and patients who refused coronary bypass surgery. In the remaining 9 patients PCPS was used as an emergency procedure, to stabilize and even resuscitate patients with acute myocardial infarction and cardiogenic shock, in order to attempt urgent PCI. RESULTS: Among the 19 patients who were treated with PCPS-supported PCI, 11 (57.9%) survived and 8 (42.1%) patients did not. ST elevation myocardial infarction with cardiogenic shock was more prevalent in the non-survivors than in the survivors (75% vs. 27.3%, p=0.04). The elective PCPS-supported PCI was practiced more frequently in the survivors than in the non-survivors (72.7% vs. 25%, p=0.04). In the analysis of the event-free survival curve between elective and emergency procedures, there was a significant difference in the survival rate (p=0.025). Among the survivors there were more patients with multi-vessel disease, but a lower Thrombolysis in Myocardial Infarction grade in the culprit lesions was detected in the non-survivors, before PCI. Although we studied high-risk patients, there was no procedure-related mortality. CONCLUSION: Our experience suggests that PCPS may be helpful in high risk patients treated with PCI, especially in elective cases. More aggressive and larger scale studies of PCPS should follow.

Outcomes of endovascular treatment of chronic total occlusion of the infrarenal aorta.

BACKGROUND: Few reports have been published on the outcomes of endovascular therapy in chronic total occlusion of the aorta. METHODS: Endovascular treatment was attempted in 49 patients (40 men and nine women; aged 64.1 ± 10.9 years) with infrarenal aortic occlusion between January 1995 and December 2009. The first attempt at wire passage and balloon angioplasty was usually performed by an antegrade approach through the brachial artery. Stents were implanted with or without intra-arterial administration of thrombolytic agents. We investigated the immediate and midterm outcomes of endovascular therapy for chronic infrarenal aortic occlusions. RESULTS: Technical success was achieved in 40 patients (81.6%). Procedural failures were due to wire passage failure in eight patients and to embolization and spinal cord infarction in one. Stents were implanted in 97.5% of patients. Major complications occurred in eight patients (16.3%): two neurologic events (spinal and cerebral infarction), two cases of jailed renal artery after stenting, and one case each of periprocedural death from pneumonia, distal embolization requiring embolectomy, iliac artery rupture requiring implantation of covered stents, and access site pseudoaneurysm treated with surgery. In patients treated successfully, the primary patency rate was 88.4% at 1 year and 80.1% at 3 years. The major amputation rate was 0%. Seven patients (17.5%) required repeat intervention (n = 5) or bypass surgery (n = 2) during the follow-up period. CONCLUSION: Endovascular therapy of infrarenal aortic occlusion was feasible in most cases, and midterm patency was favorable. However, because of relatively high procedurally related complication rates, cautious selection of patients and appropriate preventive measures are necessary to improve immediate outcomes.

Hybrid endovascular repair of thoracic aortic aneurysm in a patient with Behçet's disease following right to left carotid-carotid bypass grafting.

Endovascular repair of inflammatory aortic aneurysms has been reported as an alternative to open surgical treatment. In selective cases, adjunctive bypass surgery may be required to provide an adequate landing zone. We report a case of endovascular repair of an inflammatory aortic aneurysm in a patient with Behçet's disease using a carotid-carotid bypass graft to provide an adequate landing zone. A 45-yr-old man with a voice change was referred to our hospital with the diagnosis of saccular aneurysm of the distal aortic arch resulting from vasculitis. Computed tomography showed a thoracic aortic aneurysm with thrombosis. Right to left carotid-carotid bypass grafting was performed. After 8 days, the patient underwent an endovascular stent graft placement distal to the origin of the innominate artery. The patient was discharged with medication and without postoperative complications after 5 days. Hybrid endovascular treatment may be suitable a complementary modality for repairing inflammatory aortic aneurysms.

Efficacy of stent-supported subintimal angioplasty in the treatment of long iliac artery occlusions.

BACKGROUND: Subintimal angioplasty (SA) is becoming increasingly accepted as a revascularization technique for chronic arterial occlusive disease. However, its efficacy in iliac artery occlusions has not been established. Therefore, we investigated the procedural and clinical outcomes of subintimal angioplasty in long iliac artery occlusions and compared them with those of intraluminal angioplasty (IA) in nonocclusive stenotic iliac artery lesions. METHODS: We retrospectively analyzed data from 151 consecutive patients with long (>5 cm) iliac artery lesions (204 limbs) who underwent angioplasty with primary stent implantation from October 2004 through July 2008. Among them, 100 lesions in 100 patients were treated with intentional SA, and 104 lesions in 82 patients were treated with IA. We compared the baseline characteristics and immediate and long-term outcomes of iliac artery lesions treated with SA versus IA. RESULTS: Baseline characteristics showed that longer lesions and critical limb ischemia were found more frequently in the SA group, whereas diabetes and combined femoropopliteal lesions were present more often in the IA group. The technical success rate of SA was lower than that of IA (93.0% vs 99.0%; P = .048). However, there was no significant difference in the procedure-related complications between the SA and IA groups (4.0% vs 4.8%; P = .779). Primary patency rates for SA and IA were 96.8% and 98.0% at 1 year, and 93.9% and 90.6% at 2 years, respectively (log rank P = .656). CONCLUSION: Stent-supported SA in occlusive iliac lesions was safe and showed a high long-term patency rate comparable to that of IA performed in nonocclusive iliac lesions despite longer lesion length. Thus, SA with implantation of stents is an effective technique for the treatment of chronic long iliac artery occlusion.

Study design and rationale of "Synergistic effect of combination therapy with cilostazol and ProbUcol on plaque stabilization and lesion REgression (SECURE)" study: a double-blind randomised controlled multicenter clinical trial.

BACKGROUND: Probucol, a cholesterol-lowering agent that paradoxically also lowers high-density lipoprotein cholesterol has been shown to prevent progression of atherosclerosis. The antiplatelet agent cilostazol, which has diverse antiatherogenic properties, has also been shown to reduce restenosis in previous clinical trials. Recent experimental studies have suggested potential synergy between probucol and cilostazol in preventing atherosclerosis, possibly by suppressing inflammatory reactions and promoting cholesterol efflux. METHODS/DESIGN: The Synergistic Effect of combination therapy with Cilostazol and probUcol on plaque stabilization and lesion REgression (SECURE) study is designed as a double-blind, randomised, controlled, multicenter clinical trial to investigate the effect of cilostazol and probucol combination therapy on plaque volume and composition in comparison with cilostazol monotherapy using intravascular ultrasound and Virtual Histology. The primary end point is the change in the plaque volume of index intermediate lesions between baseline and 9-month follow-up. Secondary endpoints include change in plaque composition, neointimal growth after implantation of stents at percutaneous coronary intervention target lesions, and serum levels of lipid components and biomarkers related to atherosclerosis and inflammation. A total of 118 patients will be included in the study. DISCUSSION: The SECURE study will deliver important information on the effects of combination therapy on lipid composition and biomarkers related to atherosclerosis, thereby providing insight into the mechanisms underlying the prevention of atherosclerosis progression by cilostazol and probucol. TRIAL REGISTRATION NUMBER: ClinicalTrials (NCT): NCT01031667.