Effect of Recombinant ApoA-I Milano on Coronary Atherosclerosis in Patients With Acute Coronary Syndromes: Difference between revisions

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VisualWikitext

Revision as of 22:48, 20 September 2013

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: : Rim Halaby, M.D. [2]

Synonyms and keywords: Apo A-1 Milano, ETC 216, MDCO 216

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).^[1]

Previous studies conducted on mice and rabbits showed that rApo A-I Milano/phospholipid complex can mobilize cholesterol within 48 hours and reduce atherosclerosis.^[1]

Timeline

Timeline
Start Date	November 2001
End Date	March 2003
Status

The previous information was derived from ClinicalTrials.gov on 09/20/2013 using the identification number NCT------.

Study Description

Study Description
Study Type	Interventional
Study Phase
Study Design
Allocation	Randomaized
Endpoint
Interventional Model
Masking
Study Details
Primary Purpose
Condition
Intervention
Study Arms
Population Size

The previous information was derived from ClinicalTrials.gov on 09/20/2013 using the identification number NCT-----.

Methods

A 5 week, randomized, double-blinded, multicenter, parallel-treatment randomized control trial^[1]
Patients enrolled: 123 patients
Patients randomly assigned: 57 patients

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.

Study Arms

11 patients in placebo group consisting of 0.9% normal saline
21 patients in low (15 mg/kg) dose ETC-216 group
15 patients in high (45 mg/kg) dose ETC-216 group

The ratio of patient enrollment in the 3 groups was 1:2:2, respectively.^[1]

IVUS was done at baseline. Intravenous infusion took place weekly for 5 consecutive weeks. Two weeks after infusion, IVUS was repeated for comparison.^[1]

Outcomes

Primary Outcome

Change in percent atheroma volume as measured by IVUS^[1]

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.^[1]

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).^[1] 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).^[1]

However, luminal diameter on angiography was not different when comparing follow-up to baseline or when comparing ETC-216 vs. placebo.^[1]

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.^[1]
1 patient with chills, rigors, rash, nausea, vomiting, and diaphoresis that occurred during infusion.^[1]

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.^[1]

References

↑ ^1.00 ^1.01 ^1.02 ^1.03 ^1.04 ^1.05 ^1.06 ^1.07 ^1.08 ^1.09 ^1.10 ^1.11 ^1.12 Nissen SE, Tsunoda T, Tuzcu EM; et al. (2003). "Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial". JAMA : the Journal of the American Medical Association. 290 (17): 2292–300. doi:10.1001/jama.290.17.2292. PMID 14600188. Unknown parameter |month= ignored (help)

[pmid14600188-1] 1.00 ^1.01 ^1.02 ^1.03 ^1.04 ^1.05 ^1.06 ^1.07 ^1.08 ^1.09 ^1.10 ^1.11 ^1.12 Nissen SE, Tsunoda T, Tuzcu EM; et al. (2003). "Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial". JAMA : the Journal of the American Medical Association. 290 (17): 2292–300. doi:10.1001/jama.290.17.2292. PMID 14600188. Unknown parameter |month= ignored (help)

[1]

@@ Line 5: / Line 5: @@
 {{SK}} Apo A-1 Milano, ETC 216, MDCO 216
 ==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>
@@ Line 12: / Line 13: @@
 ==Timeline==
-===Start Date===
+{| class="wikitable" border="1" style="background:WhiteSmoke" width="40%"
-November 2001
+|-
-===End Date===
+| Colspan="2" style="background:Gainsboro" align="center"|'''Timeline'''
-March 2003
+|-
+| Style="width:30%"| '''Start Date'''||Style="width:70%"| November 2001
+|-
+| '''End Date'''||March 2003
+|-
+| '''Status'''||
+|-
+|}
+<span style="font-size:85%">The previous information was derived from ClinicalTrials.gov on 09/20/2013 using the identification number NCT------.</span>
+==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'''||
+|-
+| '''Interventional Model'''||
+|-
+| '''Masking'''||
+|-
+| Colspan="2" style="background:Gainsboro" align="center"|'''Study Details'''
+|-
+| '''Primary Purpose'''||
+|-
+| '''Condition'''||
+|-
+| '''Intervention'''||
+|-
+| '''Study Arms'''||
+|-
+| '''Population Size'''||
+|-
+|}
+<span style="font-size:85%">The previous information was derived from ClinicalTrials.gov on 09/20/2013 using the identification number NCT-----.</span>
 ==Methods==
@@ Line 21: / Line 66: @@
 *Patients enrolled: 123 patients
 *Patients randomly assigned: 57 patients
+==Eligibility Criteria==
 ===Inclusion Criteria===
 *Age: 30-75 years
@@ Line 38: / Line 83: @@
 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>
 ===Outcomes===
 ====Primary Outcome====
@@ Line 44: / Line 88: @@
 ====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==
+===Results===
 *10 patients were discontinued, while another 3 elected to discontinue
 *2 patients were withdrawn for adverse events
@@ Line 59: / Line 103: @@
 *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==
+===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>

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