New data from a 7-year study, a landmark New England Journal of Medicine update, and what it means for patients who have been told amputation is the only path forward
The statistics on no-option Chronic Limb-Threatening Ischemia have not changed enough to be comfortable. A 2025 real-world study published in Scientific Reports tracked 180 no-option CLTI patients across 22 centres in the US. At one year: 45% had undergone major amputation, and 33% had died.
For context: researchers at University Hospitals have noted that nearly half of all patients with vascular disease die within five years of a major amputation. That mortality rate exceeds five-year rates for breast cancer, colon cancer, and prostate cancer.
Most patients facing amputation do not know that statistic. They should. Because knowing it is what drives the question: what is the current state of the research, and does any of it apply to me?
What "No-Option" CLTI Actually Means
Chronic Limb-Threatening Ischemia is the most advanced stage of Peripheral Artery Disease. Blood flow to the leg has fallen so critically low that tissue cannot survive without intervention. The hallmarks are persistent night pain in the foot, non-healing wounds, and in severe cases, tissue that begins to darken and die.
The standard treatment is revascularization: restoring blood flow through bypass surgery, angioplasty, or stenting. When these work, they can be life-changing. But a substantial subset of CLTI patients cannot have them, because the arterial disease has extended too far into the small vessels of the calf and foot. There is no viable target for a bypass. No vessels accessible to a catheter. This is formally designated "no-option" CLTI.
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Real-world no-option CLTI outcomes at 1 year (CLARITI study, 2025, 22 US centres): 45% major amputation rate 33% mortality Only 37% alive without major amputation Two-thirds of survivors still had non-healing wounds |
The Research That Is Changing the Conversation
Two studies published in 2025 represent meaningful progress for patients in this situation.
In October 2025, the New England Journal of Medicine published two-year results from the PROMISE I and II trials studying transcatheter arterialization of the deep veins using the LimFlow System. At two years, 65% of no-option patients had avoided major amputation. The procedure works by redirecting oxygenated blood through the venous system to bypass blocked arteries, and it is now included in multi-speciality consensus guidelines as a consideration for no-option CLTI patients.
Separately, a September 2025 study published in PubMed followed 130 patients with diabetic foot ulcers and CLTI over 7 years, comparing outcomes in those treated with autologous cell therapy against those treated with standard care. The study found significantly longer amputation-free survival and lower major amputation rates in the cell therapy group. The authors concluded: autologous cell therapy was effective in long-term limb salvage in people with no-option CLTI.
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Important context on these findings: The TADV results are from single-arm trials, not randomized controlled trials. The cell therapy study compared against a conservative care control. Both represent meaningful scientific signals, not definitive proof of benefit for all patients. |
Where ACP-01 Fits in This Research Landscape
ACP-01 is an investigational autologous angiogenic cell therapy developed by Hemostemix. Like the cell therapy studied in the 2025 PubMed paper, it uses cells derived from the patient’s own blood, concentrated and delivered directly to ischemic tissue to stimulate new blood vessel formation.
A Phase II randomized controlled trial at Vancouver General Hospital focused on no-option CLTI patients with active ulceration. Leading with what matters most: ACP-01 achieved a 95.2% limb salvage rate and 95.2% survival at 12 months, compared with 75% limb salvage and 87.5% survival in the placebo group. That is an 81% relative risk reduction in major amputation.
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Phase II trial results: ACP-01 in no-option CLTI (Vancouver General Hospital): 95.2% limb salvage at 12 months vs. 75% in the placebo group 95.2% survival at 12 months vs. 87.5% in the placebo group 81% relative risk reduction in major amputation 83% of patients followed for up to 4.5 years maintained their outcomes Wound lesion reduction from a mean of 146 mm² to 0.48 mm² at 3 months: from the size of a wild strawberry to the size of a grain of sand Zero treatment-related serious adverse events Zero treatment-related deaths |
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Important context: These results are from a Phase II randomized controlled trial sub-analysis. ACP-01 is investigational and not approved for general clinical use by Health Canada, the FDA, or any other regulatory authority. This data represents peer-reviewed clinical evidence that research is continuing to build on. Individual outcomes vary. |
Access to ACP-01 is currently available through regulated pathways in Florida under Senate Bill 1768, in Toronto through compassionate access, and internationally in the Bahamas and Dominican Republic, for patients who meet eligibility criteria after individual evaluation.
What Patients Facing This Situation Should Do
- Seek a second opinion at a high-volume academic vascular centre before accepting that no conventional options remain. Experience varies significantly between institutions.
- Ask specifically about the transcatheter deep vein arterialization procedure if you have not already been evaluated for it. It was included in 2024 multi-specialty consensus guidelines and is available at select US centres.
- Ask directly about investigational research programs. Being evaluated for a clinical research program is a legitimate and appropriate step after conventional options have been exhausted.
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Speak with our clinical team The Hemostemix clinical team works specifically with patients who have been told no further conventional options remain. We will review your history and imaging and tell you honestly whether you may be a candidate for evaluation in our research program. Email: clawrence@hemostemix.com Call: +1 (239) 341-5842 Book: hemostemix.com/book-croom |
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Disclaimer: ACP-01 is an investigational therapy and has not been approved by Health Canada, the FDA, or any other regulatory authority for the treatment of CLTI or any other condition. This article is for educational purposes only and does not constitute medical advice. Individual outcomes vary. Always consult your physician before making any treatment decisions. |