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Aqueous Oxygen Therapy Improves ST –Segment Resolution in Anterior Myocardial Infarction PowerPoint PPT Presentation


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Aqueous Oxygen Therapy Improves ST –Segment Resolution in Anterior Myocardial Infarction. AMIHOT Phase II Clinical Study J. L. Martin, B.S. Lindsay, P.V. Oemrwasingh, D.A. Atsma, M.W. Krucoff, S.R. Dixon, A.L. Bartorelli, W.W. O’Neill, for the AMIHOT Investigators Main Line Health.

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Aqueous Oxygen Therapy Improves ST –Segment Resolution in Anterior Myocardial Infarction

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Aqueous Oxygen Therapy Improves ST –Segment Resolution in Anterior Myocardial Infarction

AMIHOT Phase II Clinical Study

J. L. Martin, B.S. Lindsay, P.V. Oemrwasingh, D.A. Atsma,

M.W. Krucoff, S.R. Dixon, A.L. Bartorelli, W.W. O’Neill,

for the AMIHOT Investigators

Main Line Health

TCT 2004

Washington DC, September 27- October 1, 2004


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Supersaturated Oxygen

Aqueous Oxygen (AO)

  • Solution of saline and hyperbaric levels (pO2~30,000 mmHg)

    of dissolved oxygen (1 ml O2/ml saline)

  • Remarkable stability (no bubble

    formation) despite high level of O2

    saturation due to the controlled delivery

    from high pressure (40 atm) to ambient blood

  • AO is mixed with the patient’s arterial blood at a ratio

    of 25 parts blood to 1 part AO (pO2>760 mmHg), and

    carried to the myocardial tissue via the plasma


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Infarct Size after AO Therapy

Pig Model

Area of necrosis

Area of risk

* p< 0.01 (vs. Auto RP)

Auto RP

% Left Ventricle

(n=6)

(n=6)

AO RP

AORP= Treatment group with 90’ AO hyperoxemic perfusion

Auto RP= Control group with normoxemic reperfusion

Spears et al. 1999


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TherOx Pilot Study

LV Function Recovery (WMSI)

*p<0.01 vs.baseline, † p=0.01

Dixon SR. J Am Coll Cardiol 2002;39:387-92


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Centro Cardiologico Monzino, Milan, Italy

OYSTER-AMI

AO in Anterior AMI

AO Treated vs. Controls

28% mean relative improvement

2.5% mean relative improvement

Bartorelli A. TCT 2002


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AO Therapy Benefits

  • Increasing O2 diffusion distance 3 to 4 timesand O2 penetration into ischemic myocardium

  • Reducing interstitial/endothelial edema

  • Reducing leukocyte activation (decreased myeloperoxidase levels)

  • Improving capillary blood flow in the IRA microcirculation

  • AO is believed to salvage myocardium by


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AMIHOT

Study Objective

  • To evaluate

    • the safety of intra-coronary hyperoxemic therapy after primary PCI for AMI

    • the efficacy of hyperoxemic reperfusion to enhance ST-segment elevation recovery, improve convalescent left ventricular function and reduce infarct size


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Study Organization

  • Principal Investigator: William W. O’Neill, MD

  • Sponsor: TherOx® Inc., Irvine, California

  • Core Laboratories

  • -Echo - Mayo Clinic, (Jae Oh, MD)

    • -Nuclear- Mayo Clinic, (Raymond J. Gibbons, MD)

    • -ECG - DCRI, (Mitchell W. Krucoff, MD)

  • DSMB: Magnus Ohman, MD (Chairman)


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Top Ten Enrollers

  • Jack L. Martin MD, Main Line Health System

  • Pranobe V. Oemrawsingh MD, Douwe Atsma, MDLeiden University Medical Center

  • William W. O’Neill MD, Simon R. Dixon MD, William Beaumont Hospital

  • Michael Chang, MD, William Marquardt MD, Mercy General Hospital

  • Shukri David, MD, Providence Hospital

  • Antonio L. Bartorelli, MD, Daniela Trabattoni, MD, Centro Cardiologico Monzino

  • James B. Hermiller, MD, Saint Vincent Hospital

  • Peter S. Fail, MD, Terrebonne General Hospital

  • Rimvydas Plenys, MD, Saint Agnes Medical Center

  • Habib Samady, MD, Michael Ragosta, MD, University Of Virginia Health System


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AMIHOT

Trial Algorithm

  • Major exclusion:

  • Cardiogenic shock

  • Need for IABP

  • Systemic pO2

  • <80mmHg

Anterior MI or

Inferior MI withanterior ST

AMI  24-hrs

(Primary or Rescue) n=269

Successful PCI

Initial TIMI flow  2

Hyperoxemic Reperfusion with AO for 90-minutes

Normoxemic Reperfusion

(Standard Therapy)

ST-Monitor 24-hours

Enrollment in 20 US and European sites

Jan 2002 – Dec 2003

SPECT Scan 14-days

Contrast Echo 1 month

Contrast Echo 3 months


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AMIHOT Trial

Endpoints

  • Primary Safety Endpoint

    • - Composite of death, reinfarction, TVR and stroke at 30 days

  • Primary Efficacy Endpoints

    • - Regional wall motion score index (WMSI) at 3 months

    • (16-segment model*)

    • - Infarct size at 14-days (SPECT imaging)

    • - ST-Segment resolution (continuous ST-monitoring)

*Schiller et al. J Am Soc Echo1989; 2: 358-367


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Control (n=135)

AO (n=134)

Age (yrs)

60.0

60

Female

27%

27%

Diabetes

11%

13%

Hypertension

49%

53%

Dyslipidemia

41%

49%

Smoker

42%

43%

Previous MI

10%

13%

Previous PCI

7%

12%

Previous CABG

1.5%

1%

Time to Reperfusion (hours)

5.45

6.23

Door to Balloon (hours)

Rescue PCI

2.23

16%

1.88

11%

Anterior MI

56%

60%

AMIHOT Trial

Clinical Characteristics


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Control (n=135)

AO (n=134)

Infarct related artery

LAD

56%

60%

RCA

36%

31%

Circumflex

Other

6%

2%

8%

1%

Initial TIMI flow grade

0/1

90%

87%

2

10%

13%

3

0%

0%

Stent

100%

100%

IIb/IIIa inhibitor

84%

90%

Final TIMI flow grade

0/1

0%

0%

2

8%

4%

3

92%

96%

AMIHOT Trial

Angiographic Characteristics


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AO system & Delivery


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Primary Safety Endpoint

6.0

%

4.4

3.0

2.2

2.2

1.5

1.5

1.5

1.5

0.7

Death

Re-Infarct

TVR

Stroke

Composite

Treat (n=134)

Control (n=135)

AMIHOT Trial - 30-day MACE

p=ns


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All Patients (Area under the Curve)

2200

Tx (n = 106)

Ctr (n = 116)

2000

1800

Area Under the Curve

Mean ST-elevation

1600

1400

1200

p = ns at 3, 4, 6 hrs

1000

3

4

5

6

t (hr)

AMIHOT ST-Elevation Reduction in

AO Therapy vs. Controls


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AMIHOT ST-Elevation Reduction

in AO Therapy vs. Controls

Anterior Patients (Area under the Curve)

3500

Tx (n = 65)

Ctr (n = 64)

3000

2500

Area Under the Curve

Mean ST-elevation

2000

1500

p = 0.04 @ 3 hrs

p = 0.03 @ 4 hrs

p = 0.02 @ 6 hrs

1000

3

4

5

6

t (hr)


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Regional Wall Motion & Infarct Size

Primary Endpoints

Infarct Size

Regional Wall Motion

P=0.16

P=NS

N=119

N=101

N=112

N=103


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Time to Reperfusion <6 hrs

All Patients

Infarct Size

Regional Wall Motion

P=0.04

P=0.05

N=84

N=69

N=82

N=69


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Regional Wall Motion

Anterior MI Patients

P=0.049

P=0.01

N=68

N=61

N=49

N=42


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AMIHOT Trial

Conclusions

gg

  • Hyperoxemic reperfusion with Aqueous Oxygen is safe and well tolerated after primary PCI for AMI

  • ST segment resolution is significantly better in the anterior MI group with a favorable trend in the entire cohort

  • Infarct size as determined by Sestamibi Scan shows a favorable trend in the entire cohort with a significant reduction in infarct size in patients treated within 6 hours of symptom onset


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AMIHOT Trial

Conclusions - continued

  • Early indicators of relief of myocardial ischemia (i.e ST-Segment resolution) lead to later functional recovery (i.e. RWMSI improvement at 3 months).

  • The AMIHOT study is the first adjunctive device study to demonstrate significance in multiple endpoints in AMI.


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