Docstoc

BE SMART

Document Sample
BE SMART Powered By Docstoc
					                                            Final Protocol 20100715




            Coronary Angioplasty in
          Octogenarians with Emergent
              Coronary Syndromes

                                 80 +

Author:   Per Albertsson MD, PhD
          Div of Cardiology
          Sahlgrenska University Hospital
          413 45 Göteborg
          Sweden




OCTOGENARIANS Version 9                                          1
                                                                     Final Protocol 20100715


1. BACKGROUND

1.1 PCI for Acute Coronary syndromes

Percutaneous Coronary Intervention (PCI) for ST-elevation Myocardial Infarction (STEMI)
and Non ST-elevation Myocardial Infarction (NSTEMI) is a Class I A indication according to
both the European Society of Cardiology and the American College of Cardiology (1,2).
Numerous randomised trials have shown that an invasive strategy will reduce adverse clinical
events in large patient groups with these syndromes. (3-5)

1.2 PCI in octogenarians with Acute Coronary Syndromes

Elderly patients have traditionally been underrepresented in clinical trials of acute coronary
syndromes (6), and few trials have been addressing the elderly population as a primary
investigational target.
Conflicting results have been shown in previous studies examine outcomes in elderly patients
with STEMI or NSTEMI. For example in a sub-analysis from the TACTICS-TIMI 18 trial
patients older than 75 years of age benefited from an invasive strategy. The absolute reduction
in death or MI at 6 months was 10.8 % (relative reduction 56%) with an invasive strategy,
compared with 6.1% for the population younger than 65 years. Major bleeding rates were
though higher with the invasive strategy in the patients older than 75 years of age, 16.6% vs.
6.5%. (7). In contrast, the senior PAMI trial could not demonstrate superior results with
angioplasty compared to thrombolysis in an elderly population with STEMI.
In current clinical practice older patients with acute coronary syndromes are less likely to
undergo invasive procedures than are younger patients (8-12).
In the Swedish registry for myocardial infarction (SWEDEHEART/RIKS-HIA 2008), only 20
% of patients with myocardial infarction older than 75 yeas old were treated with angioplasty
or bypass surgery (CABG).


2. HYPOTHESIS.
The primary objective of this study is to demonstrate that in an elderly population presenting
with acute coronary syndromes, an invasive strategy with treatment with PCI or CABG is
superior to a conservative strategy with pharmacological treatment.

2.1 Primary Endpoint

      MACCE (major adverse cardiac and cerebral events) = the composite of Death,
       Myocardial infarction, Urgent revascularisation, Recurrent hospitalisation due to
       cardiac reason and Stroke at 1 year

2.2 Secondary Endpoint

      MACCE at 1 month

      Major bleeding at 1 month




OCTOGENARIANS Version 9                                                                          2
                                                                     Final Protocol 20100715

        Minor bleeding at 1 month

        Death at 1 year

        A composite of cardiac death and myocardial infarction at 1 year

        Level of angina pectoris at 1 year

        Quality of life at 1 year


3. STUDY OVERVIEW

This study will be a multi centre trial, with a randomized design with blinded evaluation. The
study population consists of 200 patients at age >80 with acute coronary syndromes.
The treatment groups consist of:

1) Acute or sub-acute (during initial hospitalisation phase) coronary angiogram followed with
PCI or Coronary Bypass surgery when suitable, or

2) (Optimal) Medical treatment.


4. PATIENT SELECTION

4.1 Inclusion Criteria

1.             >80 years of age


2.             Acute Coronary Syndrome with ischemic symptoms (mainly chest pain) lasting
               over 10 minutes during the last 72 hours.

               AND at least one of the following:

               2.1 Ischemic ST-segment depression > 1mm

               2.2 Elevated Troponin I, or Troponin T or CK-MB


3.             Written informed consent before randomization


4.2 Exclusion Criteria

1              PCI within 30 days prior to randomization

2.             Suspected ongoing active internal bleeding



OCTOGENARIANS Version 9                                                                      3
                                                                     Final Protocol 20100715

3.            ST segment elevation of >1mm in two contiguous leads on ECG

4.            Enrolment in another study that has not completed the follow up phase.

5.            Known allergy to Aspirin or Clopidogrel

6.            Severe Dementia

7.            Expected limited 1 year survival due to other disease(s)

8.            Unwillingness to participate in the trial or expected problems with compliance


4. STUDY PLAN
4.1 Randomization procedure.

Patients will be randomised with the use of closed envelopes.

4.2 Catheterization

4.2.1 Coronary Angiography

Coronary angiography will be performed with the use of 5-8F catheters via the femoral or
radial approach to the operator’s discretion.

4.2.2 Angioplasty

Coronary angioplasty will be performed according to routine practice.

4.3 Post procedure, Hospital face

Blood tests will be performed as mentioned in paragraph 6
Adverse events will be registered according to paragraph 4.4.1
Major bleeding and minor bleeding will be registered according to paragraph 4.4.2

4.4 Discharge

Adverse Events (AE) and Serious Adverse Events (SAE) will be reported.

4.4.1 Adverse Event (AE)

An AE is any unfavourable sign or symptom associated with the study agents or the coronary
intervention.

4.4.2 Serious Adverse Event (SAE)

A SAE is any AE occurring that results in

        Death or


OCTOGENARIANS Version 9                                                                        4
                                                                       Final Protocol 20100715



      Life-threatening event or

      Prolongation of existing hospitalisation or new unplanned hospitalisation or

      Persistent or significant disability or

      Intracranial haemorrhage


4.4.2.1 Major bleeding

Major bleeding is defined as either intracranial bleeding or, a decrease in haemoglobin of
more than 50g/L or intracranial bleeding or bleeding requiring surgery.

4.4.2.2 Minor bleeding

Minor bleeding is defined as, a decrease in haemoglobin of more than 30g/L (but less than 50
g/L) or spontaneous gross hematuria or haematemesis, or haematoma or pseudoaneurysm
requiring treatment (other than surgery).

4.5 30 day follow up

Serious Adverse Events (SAE) will be reported.
Patients will be contacted by telephone.

4.6 12 month follow up

Serious Adverse Events (SAE) will be reported.
Patients will be contacted by telephone.
Assessment of angina pectoris (optional)
Assessment of Quality of life (optional)


4.8 Report of adverse events

The investigator is responsible for reporting of safety information to local authorities
according to Swedish legislation.


5. TRIAL MEDICATION
The following medication is recommended but not mandatory:
Aspirin will be administered in a maintenance dose of 75-160 mg x1 to all patients. If the
patient is previously untreated a loading dose of 160-320 mg will be given.
Clopidogrel with a loading dose of 300-600 mg will be administered as soon as possible, and
always before the coronary angiogram (13).
Treatment with a Statin is started as soon as possible.
Beta blockers are recommended as an antiischemic treatment in the absence of
contraindications. Long-term treatment is recommended in the case of reduced LV function.


OCTOGENARIANS Version 9                                                                      5
                                                                      Final Protocol 20100715

Nitroglycerin intravenous, oral, s.l. or s.b. is recommended for symptom relief if necessary.
ACE-inhibitors are indicated long-term in all patients with LVEF < 40, and in patients with
diabetes mellitus or hypertension
If angioplasty is performed, the patients will be treated according to routine clinical praxis.


6. CROSSOVER
The analysis will be done according to the intention to treat principle.
Efforts should be made to keep the initial treatment allocation.
Patients randomized to intervention will of course be transferred to medical treatment in case
of coronary anatomy unsuitable for intervention.
Patients initially treated with medication will undergo intervention in case of ischemia leading
to refractory chest pain, hemodynamic instability (including cardiogenic chock), heart failure
or life-threatening arrhythmias.



7. BLOOD CHEMISTRY

7.1 Haemoglobin

Blood samples for haemoglobin will be obtained at baseline, and if suspicion of bleeding.

7.2 Platelet count

Blood samples for platelet count will be obtained at baseline and if suspicion of bleeding

7.3 Potassium, Sodium and Kreatinin

Blood samples for Potassium, Sodium and Kreatinin will be obtained at baseline.

7.4 CK-MB and Troponin

Blood samples for CK-MB and/or TnT or TnI will be obtained at baseline, and if symptoms
of myocardial ischemia.



8. DEFINITION

8.1 Death

All cause mortality

8.2 Myocardial infarction

8.2.1 STEMI (ST-Elevation Myocardial Infarction)




OCTOGENARIANS Version 9                                                                           6
                                                                     Final Protocol 20100715

Chest pain lasting more than 10 minutes in combination with ST-segment elevation (more
than 2 mm in two anterior leads, or more than 1 mm in two inferior leads) or a new developed
Left Bundle Branch Block and elevated cardiac enzymes/biochemical markers
Or a new Q-wave in 2 continuous leads on ECG

8.2.2 NSTEMI (ST-Elevation Myocardial Infarction)

Chest pain lasting more than 10 minutes in combination with elevated cardiac
enzymes/biochemical markers

8.2.3 Myocardial infarction, Peri/Post-procedural

Myocardial infarction developing within 24 hours from PCI. Includes STEMI (see 8.2.1) and
NSTEMI (see 8.2.2) with elevated biochemical markers > 3x normal level unit

8.3 Recurrent intervention

All unplanned revascularisations after the index procedure (CABG or PCI)

8.4 Recurrent hospitalisation due to cardiac reason

All non-scheduled hospitalisations due to chest pain, previously not experienced arrhythmias
or previously not experienced congestive heart failure.

8.5 Stroke

All ischemic attacks resulting in neurological disorders including TIA (transitory ischemic
attacks)

8.6 Grade of angina pectoris - OPTIONAL

The patient’s perception of angina pectoris according to Seattle Angina Questionnaire (SAQ)

8.7 Quality of Life (QoL) - OPTIONAL

The patient’s perception of QoL according to SF 36.

8.8 Frailty Score

The physician’s perception of frailty according to the CSHA (Canadian Study of Health and
Aging) Clinical Frailty Scale (14)



9. STATISTICAL CONSIDERATION

This is a randomized multi-centre trial with blinded evaluation,
According to previous trials we expect MACE rate of 40% with the conservative strategy and
this will be reduced to 20% with an invasive strategy.



OCTOGENARIANS Version 9                                                                        7
                                                                    Final Protocol 20100715

With 80 % power and a p value of <0.05, this trial will need 82 individuals in each group. To
ensure enough patients for evaluation 200 patients will be included in the trial.
No interim analysis is planned.


10. ETHICAL CONSIDERATION
An informed consent form is prepared according to the institution of University of Göteborg
requirements for informed consent.
The study will be conducted according to the World Medical Association Declaration of
Helsinki: “Ethical Principals for Medical Research Involving Human Subjects”.
(Adopted in 1964 (Helsinki) and revised in 1975 (Tokyo), 1983 (Venice), 1989 (Hong Kong),
1996 (Somerset-West) and 2000 (Edinburgh)




OCTOGENARIANS Version 9                                                                         8
                                                                    Final Protocol 20100715

References.

1. Silber S, Albertsson P, Aviles FF, et al.
Guidelines for percutaneous coronary interventions: the task force for percutaneous coronary
interventions of the European society of cardiology.
Eur Heart J. 2005 Apr;26(8):804-47.

2. Antman EM, Anbe DT, Armstrong PW, et al.
ACC/AHA guidelines for the management of patients with ST-elevation myocardial
infarction--executive summary. A report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1999
guidelines for the management of patients with acute myocardial infarction).
J Am Coll Cardiol. 2004 Aug 4;44(3):671-719.

3. Keeley EC, Boura JA, Grines CL, et.al
Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction:
a quantitative review of 23 randomized trials.
Lancet. 2003 Jan 4;361(9351):13-20.

4. Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC
II prospective randomised multicentre study. FRagmin and Fast Revascularisation during
InStability in Coronary artery disease Investigators.
Lancet. 1999 Aug 28;354(9180):708-15.

5. Cannon CP, Weintraub WS, Demopoulos LA, et al.
TACTICS (Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or
Conservative Strategy)--Thrombolysis in Myocardial Infarction 18 Investigators.
Comparison of early invasive and conservative strategies in patients with unstable coronary
syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban.
N Engl J Med. 2001 Jun 21;344(25):1879-87.

6. Lee PY, Alexander KP, Hammill BG, et al.
 Representation of elderly persons and women in published randomized trials of acute
coronary syndromes.
JAMA. 2001 Aug 8;286(6):708-13.

7. Bach RG, Cannon CP, Weintraub WS, et al.
The effect of routine, early invasive management on outcome for elderly patients with non-
ST-segment elevation acute coronary syndromes.
Ann Intern Med. 2004 Aug 3;141(3):186-95.

8. Stone PH, Thompson B, Anderson HV, et al.
Influence of race, sex, and age on management of unstable angina and non-Q-wave
myocardial infarction: The TIMI III registry.
JAMA. 1996 Apr 10;275(14):1104-12.

9. Giugliano RP, Camargo CA Jr, Lloyd-Jones DM et al
Elderly patients receive less aggressive medical and invasive management of
unstable angina: potential impact of practice guidelines.
Arch Intern Med. 1998 May 25;158(10):1113-20.


OCTOGENARIANS Version 9                                                                        9
                                                                      Final Protocol 20100715

10. Hasdai D, Holmes DR Jr, Criger DA et al
Age and outcome after acute coronary syndromes without persistent ST-segment elevation.
Am Heart J. 2000 May;139(5):858-66.

11. Yusuf S, Flather M, Pogue J, et al for OASIS investigators
Variations between countries in invasive cardiac procedures and outcomes in
patients with suspected unstable angina or myocardial infarction without initial ST elevation.
Lancet. 1998 Aug 15;352(9127):507-14.

12. TIME Investigators.
Trial of invasive versus medical therapy in elderly patients with chronic
symptomatic coronary-artery disease (TIME): a randomised trial.
Lancet. 2001 Sep 22;358(9286):951-7.

13. Patti G, Colonna G, Pasceri V, et al.
Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural
Myocardial Infarction in Patients Undergoing Coronary Intervention. Results From the
ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty)
Study.
Circulation. 2005, Apr 26;111(16):2099-106.

14. Rockwood K, Song X, MacKnight C, et al
A global clinical measure of fitness and frailty in elderly people.
CMAJ 2005 Aug 30;173(5):489-95.




OCTOGENARIANS Version 9                                                                     10
                                                                                Final Protocol 20100715

Flow Chart


                                      Day of inclusion   Day of angioplasty   Discharge           30 days   1 year

History                                      X


ECG (12-lead)                                X                                   X


Echocardiography                             X


CK-MB or TnT or TnI                          X


Aspirin                                      X                      X            X                  X         X


Clopidogrel                                  X                      X            X                  X

Informed consent                             X

Randomization                                X

Angioplasty/Conservative                     X

Frailty Score                                X
                                                                                                              X
Quality Of Life, SF36 (Optional)             X

Angina Pectoris, SAQ (Optional)              X                                                                X
Adverse event,
If symptoms of ischemia; check CkMB                                              X                  X         X
And Troponin

Major bleed (Check Hb, TPK)                                         X            X                  X         X


OCTOGENARIANS Version 9                                                                                              11

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:4
posted:12/15/2011
language:English
pages:11