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

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VisualWikitext

Latest revision as of 14:40, 18 August 2014

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

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).^[1]

Timeline

Timeline
Start Date	November 2001
End Date	March 2003
Status	Completed

Study Description

Study Description
Study Type	Interventional
Study Phase
Study Design
Allocation	Randomaized
Endpoint	Change in % atheroma volume on intravascular ultrasound (IVUS)
Interventional Model	Parallel
Masking	Double blind
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^[1]
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.^[1]

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^[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 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 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
+==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>
-*Previous studies conducted on mice and rabbits showed that rApo A-I Milano/phospholipid complex can mobilize cholesterol within 48 hours and reduce atherosclerosis.<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==
@@ Line 21: / Line 21: @@
 | '''End Date'''||March 2003
 |-
-| '''Status'''||
+| '''Status'''||Completed
 |-
 |}
-<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==
@@ Line 40: / Line 39: @@
 | '''Allocation'''||Randomaized
 |-
-| '''Endpoint'''||
+| '''Endpoint'''||Change in % atheroma volume on intravascular ultrasound (IVUS)
 |-
 | '''Interventional Model'''||Parallel
@@ Line 48: / Line 47: @@
 | Colspan="2" style="background:Gainsboro" align="center"|'''Study Details'''
 |-
-| '''Primary Purpose'''||
+| '''Primary Purpose'''||Treatment
 |-
-| '''Condition'''||
+| '''Condition'''||Acute coronary syndromes
 |-
-| '''Intervention'''||
+| '''Intervention'''||Drug: ETC-216
 |-
-| '''Study Arms'''||
+| '''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'''||123
+| '''Population Size'''||
+*Patients enrolled: 123
+*Patients randomly assigned: 57
+*Patients completed protocol: 47
 |-
 |}
-<span style="font-size:85%">The previous information was derived from ClinicalTrials.gov on 09/20/2013 using the identification number NCT-----.</span>
 ==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 randomly assigned: 57 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===
@@ Line 76: / Line 81: @@
 *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.<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>
-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 113: / Line 111: @@
 [[Category:HDL]]
 [[Category:Clinical trials]]
+[[Category:HDLpedia]]

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