Refractory AnginaPhase 2ReACTNCT01966042
Study Protocol of Intramyocardial Injection of Autologous Bone Marrow Stem Cells for Refractory Angina
A Phase 2 study testing Local sedation, Bone Marrow Aspiration and Minithoracotomy in people with Refractory Angina, run by CellPraxis Bioengenharia Ltda. at 1 site in Brazil.
Trial summary
Therapeutic neovascularization is an innovative strategy for cardiac tissue recovery due to chronic, intense ischemia. Thus stem cell therapy has become a promising procedure for the large number of patients with refractory angina due to coronary disease, despite of the use of multiple anti-angina medications, remain… Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Refractory Angina
- What is being tested?
- Local sedation, Bone Marrow Aspiration and Minithoracotomy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteBrazil
- Study dates
- Jul 2005to Dec 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged above 21 years old;
- Documented coronary artery disease by angiography and confirmed ischemia by myocardial perfusion scintigraphy with physical or pharmacological stress;
- Class IV angina pectoris (CCSAC) that is unresponsive to optimized dose of at least two anti-anginal medications including nitrates, beta blocker, calcium channel blocker or Ranolazine) as well as aspirin or other anti-platelet agent plus statin therapy;
- Considered to not be a candidate for either percutaneous catheter or surgical myocardial revascularization due to either anatomical type, extent of coronary disease in the target vessel, or caliber of the distal vessels;
- Ejection fraction of > 45% by Transthoracic echocardiogram with Doppler by the Simpson method;
- Myocardial perfusion scintigraphy showing that the areas of myocardial ischemia supply viable tissue.
Who cannot join
- Significant Valvular Heart Disease;
- Chronic kidney disease requiring renal replacement therapy;
- Severe comorbidities associated with the reduction of life expectancy in less than 5 years;
- Ongoing abusive use of alcohol or illegal drugs (Based on the Diagnostic and Statistical Manual (DSM) IV - CAGE questionnaire);
- Positive Serologic test for HIV, Human T-cell lymphotrophic virus (HTLV), Hepatitis A, B and C;
- History of Malignant neoplasia in the last 2 years;
- Participation into other studies of cell therapy in the last year;
- Pregnancy or Breast-feeding.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Study of Intramyocardial Injection of Autologous Bone Marrow Stem Cells for Refractory Angina in Patients With Normal or Slightly Reduced Left Ventricular Function.
Therapeutic neovascularization is an innovative strategy for cardiac tissue recovery due to chronic, intense ischemia. Thus stem cell therapy has become a promising procedure for the large number of patients with refractory angina due to coronary disease, despite of the use of multiple anti-angina medications, remain severely symptomatic with disabling angina.
Stem cell therapy using autologous cells from the patient's bone marrow, has been shown to be safe and associated with improved myocardial perfusion, reducing the symptoms of advanced coronary artery disease and increasing the functional capacity of patients whose therapeutic armamentarium available today has been exhausted.
The study hypothesis was that the infusion of autologous mononuclear cells derived from the patient's bone marrow and delivered via intramyocardial injection in patients with refractory angina and normal or slightly depressed ventricular function, promote improvement in the anginal symptoms and myocardial perfusion by the inducing neoangiogenesis.
Read the detailed description
This was a phase II, non-controlled (single arm) and open label clinical trial. The study was approved by the Institutional Review Board (IRB) and all patients gave informed consent prior to participation.
Refractory angina patients were defined as those with functional class IV (angina at rest) according to the Canadian Cardiovascular Society Angina Classification (CCSAC) despite maximum medical therapy, not suitable for conventional myocardial revascularization and viable myocardium confirmed by nuclear imaging.
Patients were evaluated according to different parameters, for a total period of 12 months, and the primary objectives were:
- Improvement in functional class and angina symptoms (CCSAC) of the patients with refractory angina pectoris after the infusion of autologous bone marrow mononuclear cells after the intervention;
- Improvement in myocardial perfusion before and after cell delivery;
- Evaluate the safety of the delivery of autologous bone marrow mononuclear cells route in individuals with refractory angina.
In the screening evaluation, individuals with the presumptive diagnosis of class IV refractory angina and who met all study criteria were approached about the possibility of participating in the study by the principal investigator. Then, the patients were submitted to a baseline evaluation with a serious of blood and image tests.
The interventions were the Bone Marrow Aspiration - For each patient, a total of 100 cc of bone marrow was aspirated from the iliac crest at the time of anesthesia for their cardiac surgery - and the Infusion - After processing the cells, the surgeon delivered it by a series of epicardial injections into the left ventricular myocardium.
The processing of bone marrow autologous cells aimed to enrich the content of the bone marrow aspirate, separating the mononuclear fraction from the cells which were already differentiated.
The postoperative stage was conducted in an identical way to that of patients who undergo to a myocardial revascularization surgery. It is important to mention that both the ICU and the ward time varied according to the patient's individual evolution.
Finally, the first follow up visit took place at 1 month after the surgery. The subsequent visits were held at 3, 6 and 12 months after the procedure.
- Conditions
- Refractory Angina
- Being tested
- Local sedation, Bone Marrow Aspiration, Minithoracotomy, Autologous bone marrow mononuclear cells infusion
- Keywords
- Refractory angina, Cell Therapy, Bone Marrow, Mononuclear Cells
- Medical subject headings
- Angina Pectoris
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Local sedationProcedure or surgery
All subjects enrolled in the study underwent local sedation for bone marrow aspiration.
Bone Marrow AspirationProcedure or surgery
All subjects enrolled in the study underwent bone marrow aspiration after they had been anesthetized from the posterior iliac crest. The sample was aspirated into a series of sterile syringes and brought to the cell processing room/laboratory. The processing was in accordance to the Standard Operating Procedure developed observing Good Practice Guidelines.
MinithoracotomyProcedure or surgery
The surgical procedure used as cardiac access route was the left anterolateral thoracotomy or left anterior minithoracotomy, depending on the segment of the left ventricle to be treated, allowing the good access to the viable myocardial areas.
Autologous bone marrow mononuclear cells infusionBiological
Once the subject had his or her chest opened and the coronary anatomy reviewed by examination of the pre-operatory nuclear scan to define the area of ischemia, the surgeon drew up the cells into a series of syringes and injected the entire contents of the cell preparation in a series of injections directly into the myocardium.
| Study group | Role | What they receive |
|---|---|---|
| Stem Cell Therapy | Experimental | All subjects enrolled in the study underwent:
Local Sedation; Bone Marrow Aspiration; Minithoracotomy; Autologous bone marrow mononuclear cells infusion. Receives: Procedure: Local sedation; Procedure: Bone Marrow Aspiration; Procedure: Minithoracotomy; Biological: Autologous bone marrow mononuclear cells infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Angina Class Variation
It was evaluated in accordance with the percentage of participants that change the functional class of angina according to CCSAC (Canadian Cardiovascular Society Angina Classification - description below), after treatment. The functional class of angina was also analyzed as an ordinal variable and the median of the functional class was calculated before and after the procedure, at the time of interest (3, 6 and 12 months post treatment), in comparison to baseline, ie. value at 3 months minus value at baseline.
Screening of Functional Graduation of Stable Angina:
I - Angina only occurs after a fast or prolonged and strenuous effort during work or recreation.
II - Slight limitation to everyday activities. III - Considerable limitation of common physical activity. IV - Inability to perform any physical activity without discomfort, the symptoms can be present at rest.
Measured: 3, 6 and 12 months
Secondary outcomes (2)
Functional Change Evaluation
Analysis of Left Ventricular Ejection Fraction (in %), by echocardiogram.
Measured: Baseline and 12 months
Functional Change Evaluation
Analysis of objective improvement in myocardial ischemia (in %), by stress technetium scintigraphy.
Measured: Baseline, 6 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2013 (estimated)
- Study startJul 2005
- Primary completionNov 2011
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Refractory AnginaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- CellPraxis Bioengenharia Ltda.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cryopraxis Criobiologia Ltda., Federal University of São Paulo, University of South Florida
- Responsible party
- Sponsor
- Investigators
- Nelson A Hossne Junior, MD, PhD, Principal investigator, Federal University of São PauloEnio Buffolo, MD, PhD, Study director, Federal University of São Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01966042
- Sponsor's protocol ID
- Cell 0314/05
- Other IDs
- 0314/05
- Acronym
- ReACT
- Status last verified
- May 2014
- First submitted
- 14 Oct 2013
- Last updated
- 3 Jun 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Intramyocardial Injection of Autologous Bone Marrow Stem Cells for Refractory Angina in Patients With Normal or Slightly Reduced Left Ventricular Function.
- ClinicalTrials.gov ID
- NCT01966042
- Acronym / sponsor ID
- ReACT / Cell 0314/05
- Conditions
- Refractory Angina
- Keywords
- Refractory angina, Cell Therapy, Bone Marrow, Mononuclear Cells
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- CellPraxis Bioengenharia Ltda.Industry (pharma, biotech, devices)
- Collaborators
- Cryopraxis Criobiologia Ltda., Federal University of São Paulo, University of South Florida
- Study start
- Jul 2005
- Primary completion
- Nov 2011 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 21 Oct 2013 (estimated)
- Results
- Posted 3 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Therapeutic neovascularization is an innovative strategy for cardiac tissue recovery due to chronic, intense ischemia. Thus stem cell therapy has become a promising procedure for the large number of patients with refractory angina due to coronary disease, despite of the use of multiple anti-angina medications, remain severely symptomatic with disabling angina.
Stem cell therapy using autologous cells from the patient's bone marrow, has been shown to be safe and associated with improved myocardial perfusion, reducing the symptoms of advanced coronary artery disease and increasing the functional capacity of patients whose therapeutic armamentarium available today has been exhausted.
The study hypothesis was that the infusion of autologous mononuclear cells derived from the patient's bone marrow and delivered via intramyocardial injection in patients with refractory angina and normal or slightly depressed ventricular function, promote improvement in the anginal symptoms and myocardial perfusion by the inducing neoangiogenesis.
Detailed description
This was a phase II, non-controlled (single arm) and open label clinical trial. The study was approved by the Institutional Review Board (IRB) and all patients gave informed consent prior to participation.
Refractory angina patients were defined as those with functional class IV (angina at rest) according to the Canadian Cardiovascular Society Angina Classification (CCSAC) despite maximum medical therapy, not suitable for conventional myocardial revascularization and viable myocardium confirmed by nuclear imaging.
Patients were evaluated according to different parameters, for a total period of 12 months, and the primary objectives were:
- Improvement in functional class and angina symptoms (CCSAC) of the patients with refractory angina pectoris after the infusion of autologous bone marrow mononuclear cells after the intervention;
- Improvement in myocardial perfusion before and after cell delivery;
- Evaluate the safety of the delivery of autologous bone marrow mononuclear cells route in individuals with refractory angina.
In the screening evaluation, individuals with the presumptive diagnosis of class IV refractory angina and who met all study criteria were approached about the possibility of participating in the study by the principal investigator. Then, the patients were submitted to a baseline evaluation with a serious of blood and image tests.
The interventions were the Bone Marrow Aspiration - For each patient, a total of 100 cc of bone marrow was aspirated from the iliac crest at the time of anesthesia for their cardiac surgery - and the Infusion - After processing the cells, the surgeon delivered it by a series of epicardial injections into the left ventricular myocardium.
The processing of bone marrow autologous cells aimed to enrich the content of the bone marrow aspirate, separating the mononuclear fraction from the cells which were already differentiated.
The postoperative stage was conducted in an identical way to that of patients who undergo to a myocardial revascularization surgery. It is important to mention that both the ICU and the ward time varied according to the patient's individual evolution.
Finally, the first follow up visit took place at 1 month after the surgery. The subsequent visits were held at 3, 6 and 12 months after the procedure.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Stem Cell Therapy | Experimental | Procedure: Local sedation, Procedure: Bone Marrow Aspiration, Procedure: Minithoracotomy, Biological: Autologous bone marrow mononuclear cells infusionAll subjects enrolled in the study underwent: Local Sedation; Bone Marrow Aspiration; Minithoracotomy; Autologous bone marrow mononuclear cells infusion. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Aged above 21 years old;
- Documented coronary artery disease by angiography and confirmed ischemia by myocardial perfusion scintigraphy with physical or pharmacological stress;
- Class IV angina pectoris (CCSAC) that is unresponsive to optimized dose of at least two anti-anginal medications including nitrates, beta blocker, calcium channel blocker or Ranolazine) as well as aspirin or other anti-platelet agent plus statin therapy;
- Considered to not be a candidate for either percutaneous catheter or surgical myocardial revascularization due to either anatomical type, extent of coronary disease in the target vessel, or caliber of the distal vessels;
- Ejection fraction of > 45% by Transthoracic echocardiogram with Doppler by the Simpson method;
Key exclusion criteria (8 listed)
- Significant Valvular Heart Disease;
- Chronic kidney disease requiring renal replacement therapy;
- Severe comorbidities associated with the reduction of life expectancy in less than 5 years;
- Ongoing abusive use of alcohol or illegal drugs (Based on the Diagnostic and Statistical Manual (DSM) IV - CAGE questionnaire);
- Positive Serologic test for HIV, Human T-cell lymphotrophic virus (HTLV), Hepatitis A, B and C;
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 |
|---|---|---|
| Local sedationAll subjects enrolled in the study underwent local sedation for bone marrow aspiration. | Procedure or surgery | Stem Cell Therapy |
| Bone Marrow AspirationAll subjects enrolled in the study underwent bone marrow aspiration after they had been anesthetized from the posterior iliac crest. The sample was aspirated into a series of sterile syringes and brought to the cell processing room/laboratory. The processing was in accordance to the Standard Operating Procedure developed observing Good Practice Guidelines. | Procedure or surgery | Stem Cell Therapy |
| MinithoracotomyThe surgical procedure used as cardiac access route was the left anterolateral thoracotomy or left anterior minithoracotomy, depending on the segment of the left ventricle to be treated, allowing the good access to the viable myocardial areas. | Procedure or surgery | Stem Cell Therapy |
| Autologous bone marrow mononuclear cells infusionOnce the subject had his or her chest opened and the coronary anatomy reviewed by examination of the pre-operatory nuclear scan to define the area of ischemia, the surgeon drew up the cells into a series of syringes and injected the entire contents of the cell preparation in a series of injections directly into the myocardium. | Biological | Stem Cell Therapy |
Primary outcome
Angina Class Variation
Time frame: 3, 6 and 12 months
It was evaluated in accordance with the percentage of participants that change the functional class of angina according to CCSAC (Canadian Cardiovascular Society Angina Classification - description below), after treatment. The functional class of angina was also analyzed as an ordinal variable and the median of the functional class was calculated before and after the procedure, at the time of interest (3, 6 and 12 months post treatment), in comparison to baseline, ie. value at 3 months minus value at baseline. Screening of Functional Graduation of Stable Angina: I - Angina only occurs after a fast or prolonged and strenuous effort during work or recreation. II - Slight limitation to everyday activities. III - Considerable limitation of common physical activity. IV - Inability to perform any physical activity without discomfort, the symptoms can be present at rest.
2 secondary outcomes
Functional Change Evaluation
Time frame: Baseline and 12 months
Functional Change Evaluation
Time frame: Baseline, 6 and 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Refractory Angina
Active, not recruitingObservational study
REDUCER-I: An Observational Study of the Neovasc Reducer™ System
Angina Pectoris, Angina Pectoris, Stable
Recruiting
Efficacy of the COronary SInus Reducer in Patients With Refractory Angina II
Refractory Angina
RecruitingPhase 2
Investigational Trial to Evaluate XC001 Delivered Via an Cardiac Catheter in Subjects With Chronic Angina.
Refractory Angina, Coronary Artery Disease
Active, not recruiting
Coronary Sinus Reducer Implantation in Patients With Ischaemia and Non-obstructed Coronary Arteries and Coronary Microvascular Dysfunction.
Refractory Angina, Microvascular Angina
Not yet recruiting
Coronary Sinus Reducer Therapy for Persisting Angina
Coronary Artery Disease, Angina (Stable)
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.
Nelson A Hossne Junior, MD, PhD principal investigator
Federal University of São Paulo
Enio Buffolo, MD, PhD study director
Federal University of São Paulo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Local sedation, Bone Marrow Aspiration and Minithoracotomy in people with Refractory Angina, run by CellPraxis Bioengenharia Ltda. at 1 site in Brazil.
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 6 inclusion and 8 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 3 Jun 2014. 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 Brazil. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Angina Class Variation (time frame: 3, 6 and 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Jun 2014; AzTrials last refreshed its copy on 7 Nov 2026.