The CHI SQUARE Trial: Difference between revisions

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Latest revision as of 16:34, 15 September 2015

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

Official Title

CHI SQUARE: Can HDL Infusions Significantly Quicken Atherosclerosis Regression? A phase II, multi-center, double-blind, ascending dose, placebo-controlled, dose-finding trial of CER-001 or placebo in subjects with acute coronary syndrome.

Objective

To determine the safety and efficacy of CER-001 on atherosclerotic plaque progression and regression in patients with acute coronary syndromes.

Sponsor

Cerenis Therapeutics, SA

Timeline

Timeline
Start Date	March 2011
End Date	March 2013
Status	Complete

The previous information was derived from ClinicalTrials.gov on 09/15/2015 using the identification number NCT01201837.

Study Description

Study Description
Study Type	Interventional
Study Phase	Phase 2
Study Design
Allocation	Randomized
Endpoint	Safety/efficacy study
Interventional Model	Parallel assignment
Masking	Double Blind
Study Details
Primary Purpose	Treatment
Condition	Acute coronary syndrome
Intervention	Drug: placebo (once-weekly injection) for 6 weeks Drug: CER-001 (once-weekly injection) for 6 weeks
Study Arms	Placebo CER-001 low dose (weekly injection) CER-001 medium dose (weekly injection) CER-001 high dose(weekly injection)
Population Size	507 patients

The previous information was derived from ClinicalTrials.gov on 09/15/2015 using the identification number NCT01201837.

Eligibility Criteria

Inclusion Criteria

Age < 75 years
Patients with ACS
Angiographic evidence of CAD with suitable target coronary artery for IVUS evaluation

Exclusion Criteria

Female of child bearing potential
Weight > 120 kg
Angiographic evidence of left main artery stenosis > 50%
Uncontrolled diabetes mellitus, defined as HbA1c>10%
Triglyceride levels > 500 mg/dL
Symptomatic congestive heart failure with NYHA class III or IV or EF<35%
Uncontrolled hypertension defined as SBP>180 mmHg
Past medical history of renal disease, liver disease, metabolic disease, GI disease, or endocrine dysfunction

Outcomes

Primary Outcomes

The absolute change in total plaque volume as assessed by IVUS and QCA. The change is measured from baseline to follow-up at 3 weeks (2-5 weeks) following the final infusion of CER-001 (approximately 9 weeks following baseline measure).

Secondary Outcomes

The percent change in total plaque volume as assessed by IVUS and QCA. The change is measured from baseline to follow-up at 3 weeks (2-5 weeks) following the final infusion of CER-001 (approximately 9 weeks following baseline measure).

Publications

Primary Results Publication:

Tardif JC, Ballantyne CM, Barter P, et al. Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial. Eur Heart J. 2014;35(46):3277-86.

Results

A total of 507 patients were randomized, of which 417 had IVUS and 461 had QCA measurements.^[1]
Compared with placebo, there was no statistically significant difference in either the nominal or the percent total atheroma volume with any dose of CER-001.^[1]
The incidence of major cardiovascular events (MACE) was statistically similar across all treatment groups (8.3% (10), 13.3% (16), and 13.7% (17) in the 3 mg/kg, 6 mg/kg, and 12 mg/kg CER-001 groups respectively vs. 9.8% (12) in placebo).^[1]

Conclusion

Infusion with CER-001 is not associated with a significant reduction in coronary atherosclerosis as evaluated by IVUS and QCA.^[1]

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 Tardif JC, Ballantyne CM, Barter P, Dasseux JL, Fayad ZA, Guertin MC; et al. (2014). "Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial". Eur Heart J. 35 (46): 3277–86. doi:10.1093/eurheartj/ehu171. PMC 4258222. PMID 24780501.

[pmid24780501-1] 1.0 ^1.1 ^1.2 ^1.3 Tardif JC, Ballantyne CM, Barter P, Dasseux JL, Fayad ZA, Guertin MC; et al. (2014). "Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial". Eur Heart J. 35 (46): 3277–86. doi:10.1093/eurheartj/ehu171. PMC 4258222. PMID 24780501.

[1]

@@ Line 2: / Line 2: @@
 {{High density lipoprotein}}
-{{CMG}}
+{{CMG}}; {{AE}} {{Rim}}; {{YD}}
+==Official Title==
+CHI SQUARE: Can HDL Infusions Significantly Quicken Atherosclerosis Regression? A phase II, multi-center, double-blind, ascending dose, placebo-controlled, dose-finding trial of CER-001 or placebo in subjects with acute coronary syndrome.
 ==Objective==
+To determine the safety and efficacy of CER-001 on [[atherosclerotic plaque]] progression and regression in patients with [[acute coronary syndromes]].
-To determine the safety and efficacy of CER-001 on [[atherosclerotic plaque]] progression and regression in patients with [[acute coronary syndromes]].
+==Sponsor==
+Cerenis Therapeutics, SA
 ==Timeline==
-===Start Date===
+{| class="wikitable" border="1" style="background:WhiteSmoke" width="40%"
-March 2011
+|-
-===End Date for Final Data Collection for Primary Outcomes===
+| Colspan="2" style="background:Gainsboro" align="center"|'''Timeline'''
-December 2012
+|-
+| Style="width:30%"| '''Start Date'''||Style="width:70%"| March 2011
+|-
+| '''End Date'''||March 2013
+|-
+| '''Status'''||Complete
+|-
+|}
+<span style="font-size:85%">The previous information was derived from ClinicalTrials.gov on 09/15/2015 using the identification number NCT01201837.</span>
-===Study Completion Date===
+==Study Description==
-April 2013
-==Methods==
-*Phase II Study
-*A 5 week multicenter, double-blinded, ascending dose, placebo-controlled, dose-finding clinical trial followed by 2-5 week observational period, and long-term follow-up up to 6 months.
+{| class="wikitable" border="1" style="background:WhiteSmoke" width="40%"
-*Data from CER-001-CLIN-001 showed that single intravenous infusion of CER-001 at doses up to 45 mg/kg over 1-2 hours is effect, safe, and tolerated.
+|-
-*Estimated enrollment: Approximately 504 patients of both genders; and approximately 126 patients per group.
+| Colspan="2" style="background:Gainsboro" align="center"|'''Study Description'''
+|-
+| Style="width:30%"|'''Study Type'''|| Style="width:70%"|Interventional
+|-
+| '''Study Phase''' ||Phase 2
+|-
+| Colspan="2" style="background:Gainsboro" align="center"|'''Study Design'''
+|-
+| '''Allocation'''||Randomized
+|-
+| '''Endpoint'''||Safety/efficacy study
+|-
+| '''Interventional Model'''||Parallel assignment
+|-
+| '''Masking'''||Double Blind
+|-
+| Colspan="2" style="background:Gainsboro" align="center"|'''Study Details'''
+|-
+| '''Primary Purpose'''||Treatment
+|-
+| '''Condition'''||Acute coronary syndrome
+|-
+| '''Intervention'''||Drug: placebo (once-weekly injection) for 6 weeks<br>Drug: CER-001 (once-weekly injection) for 6 weeks
+|-
+| '''Study Arms'''||Placebo <br> CER-001 low dose (weekly injection)<br>CER-001 medium dose (weekly injection)<br>CER-001 high dose(weekly injection)
+|-
+| '''Population Size'''||507 patients
+|-
+|}
+<span style="font-size:85%">The previous information was derived from ClinicalTrials.gov on 09/15/2015 using the identification number NCT01201837.</span>
+==Eligibility Criteria==
 ===Inclusion Criteria===
 *Age < 75 years
 *Patients with ACS
-*Angiographic evidence of CAD with suitable target coronary artery for IVUS evaluation.
+*Angiographic evidence of CAD with suitable target coronary artery for IVUS evaluation
 ===Exclusion Criteria===
@@ Line 35: / Line 77: @@
 *Symptomatic congestive heart failure with NYHA class III or IV or EF<35%
 *Uncontrolled [[hypertension]] defined as SBP>180 mmHg
-*Past medical history of renal disease, liver disease, metabolic disease, GI disease, or endocrine dysfunction.
+*Past medical history of renal disease, liver disease, metabolic disease, GI disease, or endocrine dysfunction
-===Study Arms===
-*Placebo weekly injection
-*CER-001 low dose weekly injection
-*CER-001 mid dose weekly injection
-*CER-001 high dose weekly injection
-Patients undergo 6 injections in 5 weeks of therapy period. During 2-5 week observation period, patients are followed-up by an interim visit and by later follow-up IVUS visit at end of observational period. Finally, patients will visit after 6 months of observation period end for a final follow-up visit.
+==Outcomes==
+===Primary Outcomes===
+The absolute change in total plaque volume as assessed by [[IVUS]] and [[QCA]]. The change is measured from baseline to follow-up at 3 weeks (2-5 weeks) following the final infusion of CER-001 (approximately 9 weeks following baseline measure).
-===Outcomes===
+===Secondary Outcomes===
-====Primary Outcome====
+The percent change in total plaque volume as assessed by [[IVUS]] and [[QCA]]. The change is measured from baseline to follow-up at 3 weeks (2-5 weeks) following the final infusion of CER-001 (approximately 9 weeks following baseline measure).
-The time frame difference in total plaque volume and absolute change in total plaque volume by [[intravascular ultrasound]] ([[IVUS]]) after 3 weeks after final dose when compared to baseline plaque volume (9 weeks after baseline evaluation).
-==Results==
+==Publications==
-*Estimated completion rate: 75-80%
+*Primary Results Publication:
-*Approximately 98 patients per group have IVUS follow-up
+:[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4258222/ Tardif JC, Ballantyne CM, Barter P, et al. Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial. Eur Heart J. 2014;35(46):3277-86.]
-*Results have not been officially released
+===Results===
+*A total of 507 patients were randomized, of which 417 had IVUS and 461 had QCA measurements.<ref name="pmid24780501">{{cite journal| author=Tardif JC, Ballantyne CM, Barter P, Dasseux JL, Fayad ZA, Guertin MC et al.| title=Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial. | journal=Eur Heart J | year= 2014 | volume= 35 | issue= 46 | pages= 3277-86 | pmid=24780501 | doi=10.1093/eurheartj/ehu171 | pmc=PMC4258222 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24780501  }} </ref>
+*Compared with placebo, there was no statistically significant difference in either the nominal or the percent total atheroma volume with any dose of CER-001.<ref name="pmid24780501">{{cite journal| author=Tardif JC, Ballantyne CM, Barter P, Dasseux JL, Fayad ZA, Guertin MC et al.| title=Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial. | journal=Eur Heart J | year= 2014 | volume= 35 | issue= 46 | pages= 3277-86 | pmid=24780501 | doi=10.1093/eurheartj/ehu171 | pmc=PMC4258222 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24780501  }} </ref>
+*The incidence of major cardiovascular events (MACE) was statistically similar across all treatment groups (8.3% (10), 13.3% (16), and 13.7% (17) in the 3 mg/kg, 6 mg/kg, and 12 mg/kg CER-001 groups respectively vs. 9.8% (12) in placebo).<ref name="pmid24780501">{{cite journal| author=Tardif JC, Ballantyne CM, Barter P, Dasseux JL, Fayad ZA, Guertin MC et al.| title=Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial. | journal=Eur Heart J | year= 2014 | volume= 35 | issue= 46 | pages= 3277-86 | pmid=24780501 | doi=10.1093/eurheartj/ehu171 | pmc=PMC4258222 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24780501  }} </ref>
-==Conclusion==
+===Conclusion===
-Pending
+Infusion with CER-001 is not associated with a significant reduction in coronary atherosclerosis as evaluated by IVUS and QCA.<ref name="pmid24780501">{{cite journal| author=Tardif JC, Ballantyne CM, Barter P, Dasseux JL, Fayad ZA, Guertin MC et al.| title=Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial. | journal=Eur Heart J | year= 2014 | volume= 35 | issue= 46 | pages= 3277-86 | pmid=24780501 | doi=10.1093/eurheartj/ehu171 | pmc=PMC4258222 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24780501  }} </ref>
 ==References==
@@ Line 64: / Line 104: @@
 [[Category:HDL]]
 [[Category:Clinical trials]]
+[[Category:HDLpedia]]

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