View source for Effect of Recombinant ApoA-I Milano on Coronary Atherosclerosis in Patients With Acute Coronary Syndromes

__NOTOC__
{{High density lipoprotein}}

{{CMG}}; {{AE}}: {{Rim}}

{{SK}} Apo A-1 Milano, ETC 216, MDCO 216

==Official Title==
Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial

==Objective==
*To study the effects of intravenous recombinant Apo A-1 Milano/[[phospholipid]] complexes (ETC-216) on arterial plaque burden in patients with [[acute coronary syndromes]] ([[ACS]]).<ref name="pmid14600188">{{cite journal |author=Nissen SE, Tsunoda T, Tuzcu EM, ''et al.'' |title=Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=290 |issue=17 |pages=2292–300 |year=2003 |month=November |pmid=14600188 |doi=10.1001/jama.290.17.2292 |url=}}</ref>

==Timeline==
{| class="wikitable" border="1" style="background:WhiteSmoke" width="40%"
|-
| Colspan="2" style="background:Gainsboro" align="center"|'''Timeline'''
|-
| Style="width:30%"| '''Start Date'''||Style="width:70%"| November 2001
|-
| '''End Date'''||March 2003
|-
| '''Status'''||Completed
|-
|}

==Study Description==

{| class="wikitable" border="1" style="background:WhiteSmoke" width="40%"
|-
| Colspan="2" style="background:Gainsboro" align="center"|'''Study Description'''
|-
| Style="width:30%"|'''Study Type'''|| Style="width:70%"|Interventional
|-
| '''Study Phase''' ||
|-
| Colspan="2" style="background:Gainsboro" align="center"|'''Study Design'''
|-
| '''Allocation'''||Randomaized
|-
| '''Endpoint'''||Change in % atheroma volume on intravascular ultrasound (IVUS)
|-
| '''Interventional Model'''||Parallel
|-
| '''Masking'''||Double blind
|-
| Colspan="2" style="background:Gainsboro" align="center"|'''Study Details'''
|-
| '''Primary Purpose'''||Treatment
|-
| '''Condition'''||Acute coronary syndromes
|-
| '''Intervention'''||Drug: ETC-216
|-
| '''Study Arms'''||3 treatment groups in a respective ratio of approximatley 1:2:2 as follows:
*Placebo - 0.9% normal saline (11 patients)
*Low-dose ETC-216 - 15 mg/kg (21 patients)
*High-dose ETC-216 - 45 mg/kg (15 patients)
|-
| '''Population Size'''||
*Patients enrolled: 123
*Patients randomly assigned: 57
*Patients completed protocol: 47
|-
|}

==Methods==
*A 5 week, randomized, double-blinded, multicenter, parallel-treatment [[randomized control trial]]<ref name="pmid14600188">{{cite journal |author=Nissen SE, Tsunoda T, Tuzcu EM, ''et al.'' |title=Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=290 |issue=17 |pages=2292–300 |year=2003 |month=November |pmid=14600188 |doi=10.1001/jama.290.17.2292 |url=}}</ref>
*Patients enrolled: 123 patients
*Patients completed the protocol: 47 patients

IVUS was done at baseline.  [[Intravenous infusion]] took place weekly for 5 consecutive weeks.  Two weeks after infusion, [[IVUS]] was repeated for comparison.<ref name="pmid14600188">{{cite journal |author=Nissen SE, Tsunoda T, Tuzcu EM, ''et al.'' |title=Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=290 |issue=17 |pages=2292–300 |year=2003 |month=November |pmid=14600188 |doi=10.1001/jama.290.17.2292 |url=}}</ref>
==Eligibility Criteria==
===Inclusion Criteria===
*Age: 30-75 years
*[[Angiography performed]] within 14 days following [[ACS]] event.
*At least 20% luminal diameter stenosis by visual estimated required
*[[Intravascular ultrasound]] ([[IVUS]]) done within 14 days of ACS event.
*No more than 50% luminal narrowing in a segment that is at least 30 mm in length.
* No previous [[percutaneous coronary intervention]] (PCI)
*Other [[anti-lipidemic drugs]] permitted during the study as long as no introduction or new medication or change in dosage occurs within 6 weeks of study start or end date.

===Outcomes===
====Primary Outcome====
Change in percent [[atheroma]] volume as measured by [[IVUS]]<ref name="pmid14600188">{{cite journal |author=Nissen SE, Tsunoda T, Tuzcu EM, ''et al.'' |title=Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=290 |issue=17 |pages=2292–300 |year=2003 |month=November |pmid=14600188 |doi=10.1001/jama.290.17.2292 |url=}}</ref>
====Secondary Outcomes====
Assessment of [[adverse events]], quantitative angiographic changes, change in average maximal thickness or in total volume of atheroma,or atheroma volume change in most and least severely diseases 10-mm-long segments.<ref name="pmid14600188">{{cite journal |author=Nissen SE, Tsunoda T, Tuzcu EM, ''et al.'' |title=Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=290 |issue=17 |pages=2292–300 |year=2003 |month=November |pmid=14600188 |doi=10.1001/jama.290.17.2292 |url=}}</ref>
==Publications==
===Results===
*10 patients were discontinued, while another 3 elected to discontinue
*2 patients were withdrawn for adverse events
*5 had IVUS that could not be analyzed

There was a significant difference in atheroma volume, mean change in total atheroma volume and thickness in the ETC-216 groups (combined) showing a 3.17% difference (p=0.02, p<0.001, p<0.001  respectively).<ref name="pmid14600188">{{cite journal |author=Nissen SE, Tsunoda T, Tuzcu EM, ''et al.'' |title=Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=290 |issue=17 |pages=2292–300 |year=2003 |month=November |pmid=14600188 |doi=10.1001/jama.290.17.2292 |url=}}</ref> This statistical significance was not seen in patients on placebo. Most regression using ETC-216 was seen in subsegments of 10 mm long that are severely diseased, in comparison to those with only mild disease (p<0.001).<ref name="pmid14600188">{{cite journal |author=Nissen SE, Tsunoda T, Tuzcu EM, ''et al.'' |title=Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=290 |issue=17 |pages=2292–300 |year=2003 |month=November |pmid=14600188 |doi=10.1001/jama.290.17.2292 |url=}}</ref>

However, luminal diameter on angiography was not different when comparing follow-up to baseline or when comparing ETC-216 vs. placebo.<ref name="pmid14600188">{{cite journal |author=Nissen SE, Tsunoda T, Tuzcu EM, ''et al.'' |title=Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=290 |issue=17 |pages=2292–300 |year=2003 |month=November |pmid=14600188 |doi=10.1001/jama.290.17.2292 |url=}}</ref>

Adverse events included mainly minor gastrointestinal events, [[headaches]],[[arthralgias]], and [[edema]] that were found in all 3 groups.
Two important adverse events that required withdrawal were:
*1 patient with elevated [[liver function tests]] 3 times the upper normal limit with nausea vomiting, and cholelithiasis.<ref name="pmid14600188">{{cite journal |author=Nissen SE, Tsunoda T, Tuzcu EM, ''et al.'' |title=Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=290 |issue=17 |pages=2292–300 |year=2003 |month=November |pmid=14600188 |doi=10.1001/jama.290.17.2292 |url=}}</ref>
*1 patient with chills, rigors, rash, nausea, vomiting, and [[diaphoresis]] that occurred during infusion.<ref name="pmid14600188">{{cite journal |author=Nissen SE, Tsunoda T, Tuzcu EM, ''et al.'' |title=Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=290 |issue=17 |pages=2292–300 |year=2003 |month=November |pmid=14600188 |doi=10.1001/jama.290.17.2292 |url=}}</ref>

===Conclusion===
Although Apo A-1 Milano infusions resulted in a decrease in plaque burden, further study is required to assess efficacy, safety and cost-effectiveness.<ref name="pmid14600188">{{cite journal |author=Nissen SE, Tsunoda T, Tuzcu EM, ''et al.'' |title=Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=290 |issue=17 |pages=2292–300 |year=2003 |month=November |pmid=14600188 |doi=10.1001/jama.290.17.2292 |url=}}</ref>

==References==
{{Reflist|2}}

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[[Category:Lipopedia]]
[[Category:HDL]]
[[Category:Clinical trials]]
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