N/A
Completed N=180
Plasmonic Nanophotothermal Therapy of Atherosclerosis
Source: ClinicalTrials.gov NCT01270139 ↗Enrolled (actual)
180
Serious AEs
37.1%
Results posted
Aug 2012
Primary outcomePrimary: Total Atheroma Volume — 108.2; 115.6; 178 mm3 — p=<0.05
Summary
The investigators hypothesize that the nanoburning is a very challenging technique to demolish and reverse the plaque especially in combination with stem cell technologies promising the functional restoration of the vessel wall.
The completed (in July 2012) interventional three arms (n=180) first-in-man trial (the NANOM-FIM trial) assessed (NCT01270139) the safety and feasibility of two delivery techniques for nanoparticles (NP), and plasmonic photothermal therapy (PPTT) of atherosclerotic lesions. Patients were assigned in a 1:1:1 ratio to receive either (1) nano-intervention with delivery of silica-gold NP in mini-surgery implanted bioengineered on-artery patch (n=60), or (2) nano-intervention with delivery of silica-gold iron-bearing NP with targeted micro-bubbles or stem cells in hands of magnetic navigation system (n=60) versus (3) stent implantation (n=60). The primary outcome was TAV at 12 months.
The observational prospective cohort analysis (an amendment to the protocol of August 29th 2012 with a decision to extend a 1-year study for another 4 years with the assessment of the 5-year clinical outcomes both retro- and prospectively) of the long-term clinical outcomes at the intention-to-treat population of 180 patients with CAD and angiographic SYNTAX score ≤22 enrolled initially to NANOM-FIM trial will be performed at 5 years after the intervention. The primary outcome will be a MACE-free survival. The secondary outcomes will be MACE, cardiac death, TLR (target lesion revascularization) and TVR (target vessel revascularization). Imaging endpoints will be assessed pre-, post- procedure and at 12-month follow-up. Clinical endpoints will be analyzed at the baseline and at 12 and 60-month follow-up (the release of results is expected after October 2016). Parameters of nanotoxicity will be assessed. The independent adjudication analysis of the clinical outcomes is scheduled in 2017-2019.
The subset post-hoc analysis will be conducted at 1- and 5-year follow-up (by the Amendment of August 29th 2012). At the first subset, patients underwent stenting with XIENCE V stent proximal to the site of nano-intervention (n=13). Subjects in the second subset were undergone drug-coated balloon pre-dilation with further nano-technique (n=20). Lesions in patients of the third subset were not prepared for the nano-approach (n=147) (neither stenting nor balloon angioplasty). The analysis will be performed and results will be released after 2018 with the same clinical outcomes.
This project and related manuscripts were not prepared or funded in any part by a commercial organization. Nanoparticles and biomedical equipment were supplied free for the study by the non-profit Agiko and De Haar Research Task Force (Rotterdam-Amsterdam, the Netherlands). All rights of the authors are reserved. The access of the international academic or governmental organizations to the essential and primary data of the trial is restricted by the Russian governmental authorities due to the interest of the Russian Federal Security Service (FSB).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Total Atheroma Volume |
108.2; 115.6; 178 | <0.05 sig |
| PRIMARY MACE (Major Adverse Cardiovascular Events)-Free Survival |
94.3; 91.4; 90.5 | <0.05 sig |
| SECONDARY Per Cent of Fibro-fatty Component |
16.06; 16.46; 11.32 | <0.05 sig |
| SECONDARY Event Free Survival |
91.7; 81.7; 80 | <0.05 sig |
| SECONDARY Restenosis Rate |
3.33; 3.33; 10 | <0.05 sig |
| SECONDARY Late Definite Thrombosis |
0; 1.7; 6.7 | <0.05 sig |
| SECONDARY Coronary Vasomotion - Mean Lumen Diameter After Infusion of Acetylcholine 10-6 M |
4.15; 3.91; 2.88 | <0.05 sig |
| SECONDARY Per Cent Atheroma Volume |
37.8; 39.4; 52.9 | <0.05 sig |
| SECONDARY Target Lesion Revascularization |
3.3; 3.3; 6.7 | <0.05 sig |
| SECONDARY Per Cent of Fibrous Component |
48.81; 50.95; 60.38 | <0.05 sig |
| SECONDARY Per Cent of Necrotic Core |
28.47; 26.58; 25.47 | <0.05 sig |
| SECONDARY Per Cent of Calcium |
6.57; 6.01; 2.83 | <0.05 sig |
| SECONDARY Minimal Lumen Diameter |
3.08; 2.98; 2.82 | <0.05 sig |
| SECONDARY MACE |
14.3; 20.9; 22.9 | <0.05 sig |
| SECONDARY Cardiac Death |
2; 3; 3 | <0.05 sig |
| SECONDARY TLR (Target Lesion Revascularization) |
4; 5; 6 | <0.05 sig |
| SECONDARY TVR (Target Vessel Revascularization) |
10; 16; 14 | <0.05 sig |
| SECONDARY Mean Number of Membrane Defects on Membrane of Red Blood Cells |
6.12; 1.12 | <0.05 sig |
Eligibility Criteria
Inclusion Criteria
- age 45-65 years old
- male and female
- single- or multi-vessel CAD with flow-limiting lesions
- no indications for coronary artery bypass surgery (CABG)
- stable angina with indications for percutaneous coronary interventions (PCI)
- NYHA (New York Heart Association) I-III functional class of heart failure (HF)
- treated hypertension (in supine position: systole >140 mm Hg, diastole >90 mm Hg)
- de novo treated.
Exclusion Criteria
- non-compliance,
- angiographic SYNTAX score ≥23
- history of myocardial infarction (MI), unstable angina, PCI or CABG, atrial fibrillation or other dysrhythmias, stroke
- presence of indications for CABG
- presence of contraindications for PCI or CABG
- NYHA IV functional class of HF
- diabetes mellitus (in case of fasting glucose >7.0 mM/L or random glucose >11.0 mM/L)
- untreated hypertension
- asthma
- known hypersensitivity or contraindications to anti-platelet drugs
- contrast sensitivity
- participation to any drug- or intervention-investigation during the previous 60 days
Data sourced from ClinicalTrials.gov (NCT01270139). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.