Myocardial InfarctionPhase 3AMIHOT IINCT00175058
Acute Myocardial Infarction With HyperOxemic Therapy II (AMIHOT II)
A Phase 3 study testing AO Therapy (aqueous oxygen) in people with Myocardial Infarction, run by TherOx at 1 site in United States.
Trial summary
To determine whether or not HyperOxemic therapy rendered to patients (that meet the study inclusion criteria) with anterior acute myocardial infarction < 6 hours from symptom onset to reperfusion, results in a significant reduction in infarct size as measured by SPECT @ 14 days post event. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myocardial Infarction
- What is being tested?
- AO Therapy (aqueous oxygen)
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 317 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2005to May 2008
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Candidates for this study must meet ALL of the following criteria:
- Pre-PCI:
- Patient must be >= 18 years of age
- AMI must be anterior
- Patient is experiencing clinical symptoms consistent with anterior AMI of < 6 hour duration from time of symptom onset until admission to the emergency room
- Complete medical history, history of AMI, previous coronary interventions, list of medications given within last 24 hours
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- 12-lead qualifying ECG criteria: Anterior infarction (ST-segment elevation > 1 mm in two or more contiguous leads between V1 and V4 or new left bundle branch block (LBBB) with documentation of LAD system culprit lesion)
- Patient provides written, Informed Consent
- Patient and his/her physician agree to all required follow-up procedures and visits
- Women of childbearing potential who have a negative pregnancy test (applies to female patients only)
- ANGIOGRAPHIC INCLUSION CRITERIA: These are evaluated after the subject has provided signed Informed Consent but prior to randomization:
- Based on coronary anatomy, PCI is indicated for culprit lesion with anticipated use of an Intra-Coronary Stent
- TIMI 0, I, or II flow is present on the initial angiographic injection of the infarct-related artery
- Successful angioplasty as documented by < 50% diameter residual angiographic stenosis within and associated with the culprit lesion and ³ TIMI II flow and no major complications such as perforation or shock
- Documented time of reperfusion is < 6 hours from the documented time of symptom onset
Who cannot join
- Candidates will be excluded from this study if ANY of the following conditions apply:
- Pre-PCI:
- Patients with ventricular pseudoaneurysm, VSD, or papillary muscle rupture.
- Absolute contraindications to anticoagulant therapy, including hemorrhagic diathesis or thrombocytopenia
- Systemic Arterial pO2 is < 80 mmHg with supplemental oxygen
- Placement of an intra-aortic balloon pump (IABP)
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- Patient has had coronary bypass surgery during the 30 day period preceding PCI
- Severe known cardiac valvular stenosis or insufficiency, pericardial disease, or non-ischemic cardiomyopathy
- Patients requiring cardiopulmonary resuscitation for > 10 minutes
- Cardiogenic shock (SBP < 80 mm Hg for more than 30 minutes unresponsive to fluids or requiring intravenous pressors or placement of an IABP)
- Expected survival of less than 6 months due to non-cardiac condition
- Current participation in other investigational device or drug trials that have not finished the primary efficacy endpoint follow-up parameters
- Patient has had a hemorrhagic stroke during the 6 month period preceding PCI
- Physician discretion regarding unacceptability for enrollment
- ANGIOGRAPHIC EXCLUSION CRITERIA: These are evaluated after the subject has provided signed Informed Consent but prior to randomization:
- Any proximal coronary diameter stenosis > 40 % that would restrict native flow with the Tracker-38 infusion catheter in place
- Infarct-related vessels that are either saphenous vein grafts and/or small second order coronary vessels that do not supply significant areas of myocardium
- Presence of a non-stented coronary dissection upon completion of the PCI procedure
- Unprotected left main diameter stenosis > 60%
- Severe target vessel calcification or tortuosity
- Multi - vessel disease that in the judgment of the investigator is best treated with emergent or urgent CABG or additional PCI within 30 days
- In the investigator's opinion, the target vessel is unsuitable for either placing the infusion catheter or treatment with PCI
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Acute Myocardial Infarction With HyperOxemic Therapy II
To determine whether or not HyperOxemic therapy rendered to patients (that meet the study inclusion criteria) with anterior acute myocardial infarction < 6 hours from symptom onset to reperfusion, results in a significant reduction in infarct size as measured by SPECT @ 14 days post event.
Read the detailed description
The AMIHOT II clinical trial is designed as a focused study of a promising patient subset from the completed AMIHOT study. A brief synopsis of the AMIHOT experience is provided below, followed by a description of the AMIHOT II study.
The pivotal AMIHOT clinical study for the TherOx® Aqueous Oxygen (AO) System in treating post acute myocardial infarction (AMI) patients was approved by FDA on January 10, 2002 under IDE G980257/S011. The study objective was to determine whether the adjunctive administration of AO Therapy immediately after successful PCI in a group of patients presenting less than 24 hours from AMI symptom onset improves left ventricular function and reduces the area of infarction, with no increased incidence of 30-day Major Adverse Cardiac Events (MACE) when compared to a control group receiving only PCI standard-of-care treatment. 30-day MACE comprises the combined incidence of death, reinfarction, target vessel revascularization, and stroke.
Two hundred eighty-nine (289) patients were enrolled from January 16, 2002 through December 24, 2003, including 20 run-in subjects and 269 randomized patients. Three independent biomarkers (infarct size reduction, regional wall motion score improvement at three months, and reduction in ST segment elevation) were designated as co-primary endpoints to evaluate the effectiveness of AO Therapy. The study was designed to demonstrate superiority of the AO Therapy group as compared to controls for each of these endpoints, and to demonstrate non-inferiority of the AO Therapy group as compared to Control with respect to 30-day MACE. The study population was comprised of qualifying AMI patients treated with either PCI alone or with AO Therapy as an adjunct to successful PCI within 24 hours of symptom onset.
The observed 30-day MACE rates were comparable between the AO Therapy and Control groups. The AMIHOT trial results revealed positive trends for the overall study population in favor of the AO Therapy test group in each of the three co-primary endpoints. These favorable results did not demonstrate the required level of statistical significance to claim superiority. However, an examination of a pre-specified patient subset, anterior AMI subjects treated within six hours of symptom onset, showed promising results after analysis of the surrogate endpoint data, forming the basis for this IDE supplement that requests approval to conduct a new trial focused on this further defined patient population.
TherOx has designed a follow-up clinical trial focused on these anterior AMI subjects treated within six hours, utilizing a Bayesian statistical design that incorporates both the existing AMIHOT data, and the new proposed AMIHOT II study data, into a hierarchical model for combined analysis.
The key differences between the proposed AMIHOT II study and the previously conducted AMIHOT trial are:
- Focused target patient population - anterior AMI subjects revascularized within six hours of symptom onset. (AMIHOT included patients revascularized within 24 hours of symptom onset, irrespective of location of infarct.)
- Single effectiveness endpoint - infarct size reduction as measured by 14-day Tc-99m Sestamibi SPECT imaging. (AMIHOT included 3 co-primary endpoints)
- Non-inferiority comparison of 30-day MACE rates within a 6% safety delta (AMIHOT proposed an 8% delta.)
- Randomization scheme - AMIHOT II will be randomized on a 2.8:1 (AO Therapy Group: Control Group) basis, as compared to the (1:1) randomization used in AMIHOT.
The method of administration of AO Therapy and the basic design of the AO System and AO Cartridge have not changed since the approval was granted by FDA to conduct the AMIHOT trial. The IDE number for the AMIHOT II clinical proposal is consistent with AMIHOT (G980257).
- Conditions
- Myocardial Infarction
- Being tested
- AO Therapy (aqueous oxygen)
- Keywords
- Heart Attack
- Medical subject headings
- Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AO Therapy (aqueous oxygen)Device
Also called AO Therapy, SSO2 Therapy
90-min adjunctive reperfusion of hyperoxemic blood into target coronary artery, immediately following revascularization by means of PCI with stenting
| Study group | Role | What they receive |
|---|---|---|
| 1 | No intervention | Control - Patients with acute anterior myocardial infarction revascularized by means of PCI with stenting within 6 hours of onset of symptoms, no experimental intervention |
| 2 | Experimental | AO Therapy group - anterior acute myocardial infarction patients revascularized by means of PCI with stenting within 6 hours of symptom onset, receiving adjunctive infusion of hyperoxemic blood into target coronary artery for 90 minutes post-PCI. Receives: Device: AO Therapy (aqueous oxygen) |
What is being measured
The primary outcome is the main question the study is designed to answer.
A single SPECT scan will be used to determine whether or not the treatment results in a significant reduction in infarct size in the treatment group. The scan is performed 14 days post-event.
Measured: 14 +/- 7 days
Safety will be determined by comparing 30-day MACE (Major Adverse Cardiac Events) rates, where MACE is comprised by the combined incidence of death, stroke, repeat MI, and target vessel revascularization.
Measured: 30 days
Secondary outcomes (1)
ST elevation reduction will be compared between the two randomized groups at 3, 4, and 6 hours post-intervention
Measured: 3, 4, and 6 hrs post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2005 (estimated)
- Study startAug 2005
- Primary completionJun 2007
- Study completionMay 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myocardial InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 317 participants (actual)
Sponsor and investigators
- Lead sponsor
- TherOx
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00175058
- Sponsor's protocol ID
- AMIHOT II
- Acronym
- AMIHOT II
- Status last verified
- Jun 2012
- First submitted
- 9 Sep 2005
- Last updated
- 18 Jun 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Stone GW, Martin JL, de Boer MJ, Margheri M, Bramucci E, Blankenship JC, Metzger DC, Gibbons RJ, Lindsay BS, Weiner BH, Lansky AJ, Krucoff MW, Fahy M, Boscardin WJ; AMIHOT-II Trial Investigators. Effect of supersaturated oxygen delivery on infarct size after percutaneous coronary intervention in acute myocardial infarction. Circ Cardiovasc Interv. 2009 Oct;2(5):366-75. doi: 10.1161/CIRCINTERVENTIONS.108.840066. Epub 2009 Sep 15.
PubMed 20031745
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Myocardial Infarction With HyperOxemic Therapy II
- ClinicalTrials.gov ID
- NCT00175058
- Acronym / sponsor ID
- AMIHOT II / AMIHOT II
- Conditions
- Myocardial Infarction
- Keywords
- Heart Attack
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 317 participants (actual)
- Lead sponsor
- TherOxIndustry (pharma, biotech, devices)
- Study start
- Aug 2005
- Primary completion
- Jun 2007 (actual)
- Study completion
- May 2008 (actual)
- First posted
- 15 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine whether or not HyperOxemic therapy rendered to patients (that meet the study inclusion criteria) with anterior acute myocardial infarction < 6 hours from symptom onset to reperfusion, results in a significant reduction in infarct size as measured by SPECT @ 14 days post event.
Detailed description
The AMIHOT II clinical trial is designed as a focused study of a promising patient subset from the completed AMIHOT study. A brief synopsis of the AMIHOT experience is provided below, followed by a description of the AMIHOT II study.
The pivotal AMIHOT clinical study for the TherOx® Aqueous Oxygen (AO) System in treating post acute myocardial infarction (AMI) patients was approved by FDA on January 10, 2002 under IDE G980257/S011. The study objective was to determine whether the adjunctive administration of AO Therapy immediately after successful PCI in a group of patients presenting less than 24 hours from AMI symptom onset improves left ventricular function and reduces the area of infarction, with no increased incidence of 30-day Major Adverse Cardiac Events (MACE) when compared to a control group receiving only PCI standard-of-care treatment. 30-day MACE comprises the combined incidence of death, reinfarction, target vessel revascularization, and stroke.
Two hundred eighty-nine (289) patients were enrolled from January 16, 2002 through December 24, 2003, including 20 run-in subjects and 269 randomized patients. Three independent biomarkers (infarct size reduction, regional wall motion score improvement at three months, and reduction in ST segment elevation) were designated as co-primary endpoints to evaluate the effectiveness of AO Therapy. The study was designed to demonstrate superiority of the AO Therapy group as compared to controls for each of these endpoints, and to demonstrate non-inferiority of the AO Therapy group as compared to Control with respect to 30-day MACE. The study population was comprised of qualifying AMI patients treated with either PCI alone or with AO Therapy as an adjunct to successful PCI within 24 hours of symptom onset.
The observed 30-day MACE rates were comparable between the AO Therapy and Control groups. The AMIHOT trial results revealed positive trends for the overall study population in favor of the AO Therapy test group in each of the three co-primary endpoints. These favorable results did not demonstrate the required level of statistical significance to claim superiority. However, an examination of a pre-specified patient subset, anterior AMI subjects treated within six hours of symptom onset, showed promising results after analysis of the surrogate endpoint data, forming the basis for this IDE supplement that requests approval to conduct a new trial focused on this further defined patient population.
TherOx has designed a follow-up clinical trial focused on these anterior AMI subjects treated within six hours, utilizing a Bayesian statistical design that incorporates both the existing AMIHOT data, and the new proposed AMIHOT II study data, into a hierarchical model for combined analysis.
The key differences between the proposed AMIHOT II study and the previously conducted AMIHOT trial are:
- Focused target patient population - anterior AMI subjects revascularized within six hours of symptom onset. (AMIHOT included patients revascularized within 24 hours of symptom onset, irrespective of location of infarct.)
- Single effectiveness endpoint - infarct size reduction as measured by 14-day Tc-99m Sestamibi SPECT imaging. (AMIHOT included 3 co-primary endpoints)
- Non-inferiority comparison of 30-day MACE rates within a 6% safety delta (AMIHOT proposed an 8% delta.)
- Randomization scheme - AMIHOT II will be randomized on a 2.8:1 (AO Therapy Group: Control Group) basis, as compared to the (1:1) randomization used in AMIHOT.
The method of administration of AO Therapy and the basic design of the AO System and AO Cartridge have not changed since the approval was granted by FDA to conduct the AMIHOT trial. The IDE number for the AMIHOT II clinical proposal is consistent with AMIHOT (G980257).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | No intervention | –Control - Patients with acute anterior myocardial infarction revascularized by means of PCI with stenting within 6 hours of onset of symptoms, no experimental intervention |
| 2 | Experimental | Device: AO Therapy (aqueous oxygen)AO Therapy group - anterior acute myocardial infarction patients revascularized by means of PCI with stenting within 6 hours of symptom onset, receiving adjunctive infusion of hyperoxemic blood into target coronary artery for 90 minutes post-PCI. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patient must be >= 18 years of age
- AMI must be anterior
- Patient is experiencing clinical symptoms consistent with anterior AMI of < 6 hour duration from time of symptom onset until admission to the emergency room
- Complete medical history, history of AMI, previous coronary interventions, list of medications given within last 24 hours
- 12-lead qualifying ECG criteria: Anterior infarction (ST-segment elevation > 1 mm in two or more contiguous leads between V1 and V4 or new left bundle branch block (LBBB) with documentation of LAD system culprit lesion)
Key exclusion criteria (22 listed)
- Patients with ventricular pseudoaneurysm, VSD, or papillary muscle rupture.
- Absolute contraindications to anticoagulant therapy, including hemorrhagic diathesis or thrombocytopenia
- Systemic Arterial pO2 is < 80 mmHg with supplemental oxygen
- Placement of an intra-aortic balloon pump (IABP)
- Patient has had coronary bypass surgery during the 30 day period preceding PCI
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AO Therapy (aqueous oxygen)Also: AO Therapy, SSO2 Therapy90-min adjunctive reperfusion of hyperoxemic blood into target coronary artery, immediately following revascularization by means of PCI with stenting | Device | 2 |
Primary outcome
A single SPECT scan will be used to determine whether or not the treatment results in a significant reduction in infarct size in the treatment group. The scan is performed 14 days post-event.
Time frame: 14 +/- 7 days
Safety will be determined by comparing 30-day MACE (Major Adverse Cardiac Events) rates, where MACE is comprised by the combined incidence of death, stroke, repeat MI, and target vessel revascularization.
Time frame: 30 days
1 secondary outcome
ST elevation reduction will be compared between the two randomized groups at 3, 4, and 6 hours post-intervention
Time frame: 3, 4, and 6 hrs post-intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2012.
- Derived from this study: PubMed 20031745Stone GW, Martin JL, de Boer MJ, Margheri M, Bramucci E, Blankenship JC, Metzger DC, Gibbons RJ, Lindsay BS, Weiner BH, Lansky AJ, Krucoff MW, Fahy M, Boscardin WJ; AMIHOT-II Trial Investigators. Effect of supersaturated oxygen delivery on infarct size after percutaneous coronary intervention in acute myocardial infarction. Circ Cardiovasc Interv. 2009 Oct;2(5):366-75. doi: 10.1161/CIRCINTERVENTIONS.108.840066. Epub 2009 Sep 15.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AO Therapy (aqueous oxygen) in people with Myocardial Infarction, run by TherOx at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
A single SPECT scan will be used to determine whether or not the treatment results in a significant reduction in infarct size in the treatment group. The scan is performed 14 days post-event. (time frame: 14 +/- 7 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00175058, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2012.