Table 3.
Stem cell trials with intramyocardial delivery route in patients with ischaemic cardiomyopathy
| Author/acronym, publication dates, number of patients (trial design) | Disease and delivery route | Cell type and dose | Methods for efficacy measurement | Phase, results |
|---|---|---|---|---|
|
FOCUS‐HF27: 06/2011, 30 (randomized 2:1) |
CICM (EF < 40%), IM (NOGA) |
Autologous BMMC (30 × 106 ± 0 cells) vs. control |
Symptom reduction, Echo, SPECT |
Phase II, quality of life improved at 6 months (P = 0.009), no effect on cardiac function |
|
TABMMI5: 11/2011, 20 (non‐randomized) |
CICM (EF ≤ 40%), IM (TESI) |
Autologous BMMC, CD34+, CD133+ (96 ± 29 × 106 cells) |
Symptom reduction, Echo |
Phase II, exercise tolerance test improved (P < 0.01), EF improved (from 34.9 ± 4.3 to 41.9 ± 5.1 at12 months and 42.2 ± 7.1% at 24 months, P = 0.00005) |
|
ALSTER‐Stem Cell17: 10/2012, 23 (non‐randomized) |
3–4 weeks after acute myocardial infarction (EF < 45%), IM (NOGA) |
Autologous BMMC (220 ± 42 × 106 cells) | MRI | Phase II, EF (+7.9 ± 1.5%, P = 0.001) at 6 months, no effect on scar volume |
|
POSEIDON2: 12/2012, 30 (randomized, 5 patients each dose level and cell type) |
CICM (EF < 50%), IM (TESI) |
Autologous vs. allogeneic BM‐MSC (20, 100, 200 × 106 cells) |
Symptom reduction, ESP, CT |
Phase I/II, reduced infarct scar and end‐diastolic diameter (P = 0.001) at 13 months in both groups, no effect on EF. Symptom reduction in the autologous cell group. Inverse dose response to EF and LVESV |
| MSC‐HF4: 07/2015, 60 (randomized 2:1, double‐blind, placebo‐controlled) |
CICM (EF < 45%), IM (NOGA) |
Autologous BM‐MSC (77.5 ± 67.9 × 106 cells) vs. placebo | Symptom reduction, MRI, CT |
Phase II, improvement of LVESV –7.6 ± 13.2 mL (P = 0.001), EF +5.0 ± 3.8% and stroke volume + 15.6 ± 14.6 mL (P < 0.0001) at 6 months in the cell group, no significant symptom reduction |
|
Perin et al.3: 08/2015, 60 (20 randomized patients each dose, 2:1 vs. control) |
CICM (EF < 40%), IM (NOGA) |
Allogeneic BM‐MSC (25, 75, 150 × 106 cells) | Symptom reduction, Echo, SPECT | Phase II, HF‐MACE reduced at 36 months in 150 × 106 cell group (P = 0.025) |
|
MyStromalCell18: 11/2017, 10 (non‐randomized) |
CICM (EF ≤ 45%), IM (NOGA) |
Autologous ASC (100 × 106 cells) | Safety Labs, Echo, CT | Phase II, tendency towards efficacy |
| TRIDENT29: 11/2017, 30 (randomized 1:1, double‐blind) |
CICM (EF ≤ 50%), IM (TESI) |
Allogeneic BM‐MSC (20 or 100 × 106 cells) | Symptom reduction, CT, ESP | Phase II, reduced scar size in both groups (20 × 106 P = 0.001, 100 × 106 P = 0.0002), EF increased only in 100 × 106 cell group at 12 months (+3.7 U; IQR 1.1–6.1; P = 0.04) |
|
Kastrup et al.30: ongoing, 81 (randomized 2:1, double‐blind, placebo‐controlled) |
CICM (EF ≤ 45%), IM (NOGA) |
CSCC_ASC (110 × 106 cells) vs. placebo | Echo, MRI, CT | Phase II |
| IxCELL‐DCM25: 04/2016, 126 (randomized 1:1, double‐blind, placebo‐controlled) |
CICM (EF ≤ 35%), IM (NOGA) |
Autologous Ixmyelocel‐T cell product (CD90+ MSC and CD45+, CD14+ auto‐ fluorescent+ activated macrophages, cell number not applicable) | Symptom reduction, Echo | Primary endpoint (composite number of deaths, cardiovascular hospitalizations during 12‐month follow‐up) significantly reduced (P = 0.03), no effect on EF or LVESV |
| CHART‐128: 12/2016, 315 (randomized 1:1, double‐blind, sham‐controlled) |
CICM (EF ≤ 35%), IM (C‐Cathez™) |
Autologous BM‐derived cardiopoietic cells (>24 × 106 cells) | Symptom reduction, Echo | Hierarchical composite (mortality, worsening HF, Minnesota Living with Heart Failure Questionnaire score, 6‐minute walk test, LVESV, and EF) at 9 months neutral (P = 0.27) |
| ATHENA26: 02/2017, 31, (randomized 2:1, double‐blind, placebo‐controlled) |
CICM (EF 20–45%), IM (NOGA) |
Autologous ASC (n = 28: 40 × 106 and n = 3: 80 × 106 cells) | Symptom reduction, Echo, ESP | VO2 max favoured ASC, fewer hospitalizations and symptom reduction in the ASC arm, no difference in EF and LVESV |
ASC, adipose‐derived mesenchymal stromal cells; BM, bone marrow; BMMC, bone marrow mononuclear cells; BM‐MSC, bone marrow‐derived mesenchymal stem cells; CICM, chronic ischaemic cardiomyopathy; CSCC_ASC, Cardiology Stem Cell Centre Adipose‐derived Stromal Cells; CT, computed tomography; Echo, echocardiography; EF, ejection fraction; ESP, ergospirometry; HF, heart failure; IM, intramyocardial; IQR, interquartile range; LVESV, left ventricular end‐systolic volume; MACE, major adverse cardiac events; MRI, magnetic resonance imaging; VO2, oxygen uptake; SPECT, single photon emission computed tomography.