Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12605000050651
Ethics application status
Approved
Date submitted
21/07/2005
Date registered
26/07/2005
Date last updated
26/07/2005
Type of registration
Retrospectively registered

Titles & IDs
Public title
Granulocyte-colony stimulating factor (G-CSF) mobilised autologous endothelial progenitor cells for refractory ischaemic heart disease
Scientific title
Granulocyte-colony stimulating factor (G-CSF) mobilised autologous endothelial progenitor cells for refractory ischaemic heart disease
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Patients with chronic ischaemic heart disease (IHD) on maximal medical therapy, who are not amenable to conventional revascularisation. 121 0
Condition category
Condition code
Cardiovascular 136 136 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
After baseline cardiac assessment (CA) [Seattle Angina Questionnaire (SAQ), Bruce exercise stress test (EST), persantin-Sestamibi and dobutamine-echocardiographic imaging], stable 'no option' IHD patients receive open-label G-CSF 10microg/kg for 5 days, with an EST (to facilitate myocardial cytokine generation and stem cell trafficking) on the 4th and 6th days. After 3 months, CA and the same regimen of G-CSF and ESTs is repeated, but in addition, leucopheresis and a randomized double-blinded intracoronary infusion of either CD133+ or unselected cells is performed. Final CA is 3 months thereafter.
Intervention code [1] 45 0
Treatment: Other
Comparator / control treatment
Control group
Placebo

Outcomes
Primary outcome [1] 172 0
To assess the safety of G-CSF administration in 20 stable 'no-option' patients with refractory IHD.
Timepoint [1] 172 0
Secondary outcome [1] 377 0
In this group of 20 'no-option' patients, to assess:
(I) the efficacy of G-CSF therapy (alone);
Timepoint [1] 377 0
Secondary outcome [2] 378 0
(II) the efficacy of an intracoronary infusion of endothelial progenitor cells (as defined by the surface marker CD133);
Timepoint [2] 378 0
Secondary outcome [3] 379 0
(III) the ex vivo properties of CD133+ cells.
Timepoint [3] 379 0

Eligibility
Key inclusion criteria
1. Angiographically documented coronary artery disease, not amenable to other forms of revascularisation. 2. Patients with chronic angina who have been classified according to the Canadian Cardiovascular Society Grading Scale for angina as class III or IV. 3. Age >21 years and must be mentally competent. 4. Subjects will be at maximum tolerable medical therapy for angina pectoris and will not be candidates for other therapy, such as bypass graft surgery or percutaneous interventional therapy.
Minimum age
21 Years
Maximum age
Not stated
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with uncontrolled heart failure.2. Patients with a left ventricular ejection fraction of <20% (by nuclear scanning, echocardiography or angiography).3. Patients who have had a myocardial infarction within 3 months.4. Patients with unstable angina.5. Patients with a history of serious ventricular arrhythmias who are currently taking medications for that indication or who have an automatic implantable cardiac defibrillator (AICD).6. Presence of diabetic retinopathy. This will be excluded on the basis of a formal evaluation of all diabetic patients by a specialist ophthalmologist, including fluorescein angiography, to exclude active (within the last 3 month) proliferative diabetic retinopathy.7. Current or prior history of neoplasia.8. Vulnerable populations including minors, prisoners, persons who are institutionalised or who are unable to give informed consent.9. Patients with other medical or psychiatric problems, which in the opinion of the investigator preclude them from participating in the study.10. Patients unwilling to return for follow up visits.11. Patients participating in another experimental protocol.12. Patients who are pregnant or breast-feeding.13. Claustrophobia or orthopaedic difficulties that would impede nuclear scanning.14. Patients must be deemed haemodynamically stable:-Minimum systolic blood pressure of 90mm Hg -Urine output less than 0.5cc/kg/hr for a period of eighteen hours or greater would exclude patient from study -Patients cannot be using inotropic agents such as dopamine, dobutamine, levophed, adrenaline, noradrenaline, amrinone, or milrinone.15. Patients must not have signs, symptoms or biochemical evidence of multi-organ failure.16. Patients must not have a significant active infection which is uncontrolled by antibiotic, antiviral or antifungal therapy at entry into the study, or at the time of subsequent leukopharesis procedures.17. Minimum hemoglobin of 8.0g/dl, white blood cell of 2,000/mm3 and platelet count of 100,000/mm3.18. Patients who are either candidates for, or who have received a Left Ventricular Assist Device.19. Patients who have received a heart or other organ transplant.20. Patients taking any form of immunosuppressant medication (including systemic steroids), for whatever reason.21. Patients who are candidates for heart transplantation. Such patients must not be either on the active transplant waiting list, or be under consideration for enrolment on the waiting list.22. Intolerance or allergy to HMG Co-A reductase inhibitors.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
sealed envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
20 typed A4 pieces of paper were generated; 10 with "CD133 cells" and 10 with "unselected cells" typed onto the page. These pieces of paper were then folded and placed individually into identical envelopes. The cell aloocation was not visible through the envelope. Envelopes were shuffled and an envelope is then drawn from this pile to allocate the treatment arm.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Only the intracoronary cell infusion of this trial is randomised and double-blinded. The G-CSF therapy is open label and received by all subjects.
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
19/01/2004
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 187 0
Charities/Societies/Foundations
Name [1] 187 0
The St Vincent's Clinic Foundation
Country [1] 187 0
Australia
Funding source category [2] 188 0
Charities/Societies/Foundations
Name [2] 188 0
the RT Hall Estate
Country [2] 188 0
Australia
Funding source category [3] 189 0
Charities/Societies/Foundations
Name [3] 189 0
the Macquarie Foundation
Country [3] 189 0
Australia
Primary sponsor type
Other
Name
The Victor Chang Cardiac Research Institute
Address
Country
Australia
Secondary sponsor category [1] 140 0
Hospital
Name [1] 140 0
St Vincent's Hospital, Sydney.
Address [1] 140 0
Country [1] 140 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 952 0
St Vinccen't Hospital
Ethics committee address [1] 952 0
Ethics committee country [1] 952 0
Australia
Date submitted for ethics approval [1] 952 0
Approval date [1] 952 0
Ethics approval number [1] 952 0

Summary
Brief summary
Approval granted to commence the trial in late 2003. The trial is conducted with the oversight of an independant data and safety monitoring board.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 36354 0
Address 36354 0
Country 36354 0
Phone 36354 0
Fax 36354 0
Email 36354 0
Contact person for public queries
Name 9234 0
Dr. Jason Kovacic
Address 9234 0
Victor Chang Cardiac Research Institute
384 Victoria Street
Darlinghurst NSW 2010
Country 9234 0
Australia
Phone 9234 0
+61 2 83821111
Fax 9234 0
Email 9234 0
[email protected]
Contact person for scientific queries
Name 162 0
Prof. Robert Graham
Address 162 0
Victor Chang Cardiac Research Institute
384 Victoria Street
Darlinghurst NSW 2010
Country 162 0
Australia
Phone 162 0
+61 2 92958500
Fax 162 0
Email 162 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.