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Jan Apelqvist - One of the best experts on this subject based on the ideXlab platform.
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performance of prognostic markers in the prediction of wound healing or amputation among patients with foot ulcers in diabetes a systematic review
Diabetes-metabolism Research and Reviews, 2020Co-Authors: Rachael O Forsythe, Jan Apelqvist, Edward J Boyko, Robert Fitridge, Joon Pio Hong, Konstantinos Katsanos, Joseph L Mills, Sigrid Nikol, Jim A Reekers, Maarit VenermoAbstract:Prediction of wound healing and major amputation in patients with diabetic foot ulceration is clinically important to stratify risk and target interventions for limb salvage. No consensus exists as to which measure of peripheral artery disease (PAD) can best predict outcomes. To evaluate the prognostic utility of index PAD measures for the prediction of healing and/or major amputation among patients with active diabetic foot ulceration, two reviewers independently screened potential studies for inclusion. Two further reviewers independently extracted study data and performed an assessment of methodological quality using the Quality in Prognostic Studies instrument. Of 9476 citations reviewed, 11 studies reporting on 9 markers of PAD met the inclusion criteria. Annualized healing rates varied from 18% to 61%; corresponding major amputation rates varied from 3% to 19%. Among 10 studies, skin perfusion Pressure ≥ 40 mmHg, toe Pressure ≥ 30 mmHg (and ≥ 45 mmHg) and transcutaneous Pressure of oxygen (TcPO2 ) ≥ 25 mmHg were associated with at least a 25% higher chance of healing. Four studies evaluated PAD measures for predicting major amputation. Ankle Pressure < 70 mmHg and fluorescein toe slope < 18 units each increased the likelihood of major amputation by around 25%. The combined test of Ankle Pressure < 50 mmHg or an Ankle brachial index (ABI) < 0.5 increased the likelihood of major amputation by approximately 40%. Among patients with diabetic foot ulceration, the measurement of skin perfusion Pressures, toe Pressures and TcPO2 appear to be more useful in predicting ulcer healing than Ankle Pressures or the ABI. Conversely, an Ankle Pressure of < 50 mmHg or an ABI < 0.5 is associated with a significant increase in the incidence of major amputation.
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iwgdf guidance on the diagnosis prognosis and management of peripheral artery disease in patients with foot ulcers in diabetes
Diabetes-metabolism Research and Reviews, 2016Co-Authors: Robert J Hinchliffe, Jan Apelqvist, Edward J Boyko, Robert Fitridge, Joseph L Mills, Jim A Reekers, Jack Brownrigg, C P Shearman, R E Zierler, Nicolaas C SchaperAbstract:Recommendations Examine a patient with diabetes annually for the presence of peripheral artery disease (PAD); this should include, at a minimum, taking a history and palpating foot pulses. (GRADE strength of recommendation: strong; quality of evidence: low) Evaluate a patient with diabetes and a foot ulcer for the presence of PAD. Determine, as part of this examination, Ankle or pedal Doppler arterial waveforms; measure both Ankle systolic Pressure and systolic Ankle brachial index (ABI). (strong; low) We recommend the use of bedside non-invasive tests to exclude PAD. No single modality has been shown to be optimal. Measuring ABI (with <0.9 considered abnormal) is useful for the detection of PAD. Tests that largely exclude PAD are the presence of ABI 0.9–1.3, toe brachial index ≥0.75 and the presence of triphasic pedal Doppler arterial waveforms. (strong; low) In patients with a foot ulcer in diabetes and PAD, no specific symptoms or signs of PAD reliably predict healing of the ulcer. However, one of the following simple bedside tests should be used to inform the patient and healthcare professional about the healing potential of the ulcer. Any of the following findings increases the pre-test probability of healing by at least 25%: a skin perfusion Pressure ≥40 mmHg, a toe Pressure ≥30 mmHg or a transcutaneous oxygen Pressure (TcPO2) ≥25 mmHg. (strong; moderate) Consider urgent vascular imaging and revascularisation in patients with a foot ulcer in diabetes where the toe Pressure is <30 mmHg or the TcPO2 <25 mmHg. (strong; low) Consider vascular imaging and revascularisation in all patients with a foot ulcer in diabetes and PAD, irrespective of the results of bedside tests, when the ulcer does not improve within 6 weeks despite optimal management. (strong; low) Diabetic microangiopathy should not be considered to be the cause of poor wound healing in patients with a foot ulcer. (strong; low) In patients with a non-healing ulcer with either an Ankle Pressure <50 mmHg or ABI <0.5, consider urgent vascular imaging and revascularisation. (strong; moderate) Colour Doppler ultrasound, computed tomography angiography, magnetic resonance angiography or intra-arterial digital subtraction angiography can each be used to obtain anatomical information when revascularisation is being considered. The entire lower extremity arterial circulation should be evaluated, with detailed visualisation of below-the-knee and pedal arteries. (strong; low) The aim of revascularisation is to restore direct flow to at least one of the foot arteries, preferably the artery that supplies the anatomical region of the wound, with the aim of achieving a minimum skin perfusion Pressure ≥40 mmHg, a toe Pressure ≥30 mmHg or a TcPO2 ≥25 mmHg. (strong; low) A centre treating patients with a foot ulcer in diabetes should have the expertise in and rapid access to facilities necessary to diagnose and treat PAD; both endovascular techniques and bypass surgery should be available. (strong; low) There is inadequate evidence to establish which revascularisation technique is superior, and decisions should be made in a multidisciplinary team on a number of individual factors, such as morphological distribution of PAD, availability of autogenous vein, patient co-morbidities and local expertise. (strong; low) After a revascularisation procedure for a foot ulcer in diabetes, the patient should be treated by a multidisciplinary team as part of a comprehensive care plan. (strong; low) Patients with signs of PAD and a foot infection are at particularly high risk for major limb amputation and require emergency treatment. (strong; moderate) Avoid revascularisation in patients in whom, from the patient perspective, the risk–benefit ratio for the probability of success is unfavourable. (strong; low) All patients with diabetes and an ischaemic foot ulcer should receive aggressive cardiovascular risk management including support for cessation of smoking, treatment of hypertension and prescription of a statin as well as low-dose aspirin or clopidogrel. (strong; low)
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early revascularization after admittance to a diabetic foot center affects the healing probability of ischemic foot ulcer in patients with diabetes
European Journal of Vascular and Endovascular Surgery, 2014Co-Authors: Targ Elgzyri, Johan Thorne, Karlfredrik Eriksson, Per Nyberg, Jan Larsson, Jan ApelqvistAbstract:WHAT THIS PAPER ADDS This is, to the author’s knowledge, the first study that examines the influence of time to revascularization on outcome of ischemic foot ulcers in patients with diabetes. This study observed consecutively presenting and prospectively followed patients with diabetes, foot ulcers, and severe PAD, treated and followed by a multidisciplinary foot team. Shorter time to revascularization and less tissue destruction positively affects the probability of healing over time of ischemic foot ulcer in patients with diabetes.The present study highlights the need to prioritize investigation and revascularization in patients with diabetes and peripheral ischemia to improve the outcome of foot ulcer. Objectives: There is limited information about whether time from recognition of decreased perfusion to revascularization affects the probability of healing in a patient with a diabetic foot ulcer. The aim of the present study was to examine whether time to revascularization after referral to a multidisciplinary foot center was related to the outcome of foot ulcers in patients with diabetes and severe peripheral arterial disease (PAD). Methods: Patients with diabetes, a foot ulcer, and a systolic toe Pressure <45 mmHg or an Ankle Pressure <80 mmHg were prospectively included at the foot center, and considered for revascularization according to a preset protocol. All patients underwent invasive revascularization, either percutaneous transluminal angioplasty (PTA) or reconstructive vascular surgery. All patients had continuous follow-up until healing or death irrespective of the type of revascularization. Results: A total of 478 patients were included (age 74 [range 66e80] years, 60% males), of whom 315 patients (66%) had PTA, and 163 (34%) had reconstructive surgery. Of the 478 patients, 217 (45%) healed primarily, 88 (19%) healed after a minor amputation, 76 (16%) healed after a major amputation and 92 patients (19%) died unhealed. The median time from inclusion in the study to revascularization was 8 weeks (3e18 weeks). Time to vascular intervention within 8 weeks (p < .001), maximum Wagner grade reached < 3( p < .001), absence of peripheral edema (p ¼ .033), and presence of intermittent claudication (p ¼ .001) were related to a higher probability of healing. Conclusions: Time to revascularization and extent of tissue damage were related to the probability of healing of ischemic foot ulcer in patients with diabetes over time. In the presence of a decreased perfusion in a patient with diabetes and a foot ulcer not only revascularization per se but also timing of revascularization is important for the possibility of healing without a major amputation.
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factors related to outcome of neuroischemic ischemic foot ulcer in diabetic patients
Journal of Vascular Surgery, 2011Co-Authors: Jan Apelqvist, Targ Elgzyri, Per Nyberg, Magnus Löndahl, Jan Larsson, Johan ThorneAbstract:OBJECTIVES: Peripheral vascular disease (PVD) is an important limiting factor for healing in neuroischemic or ischemic diabetic foot ulcer. The purpose of this study was to identify factors related to healing in patients with diabetes with foot ulcers and severe PVD. METHODS: Patients with diabetes with a foot ulcer, consecutively presenting at a multidisciplinary foot center with a systolic toe Pressure <45 mm Hg or an Ankle Pressure <80 mm Hg were prospectively included, followed according to a preset program, and with the exception of specified exclusions, subjected to angiography offered vascular intervention when applicable. All patients had continuous follow-up until healing or death irrespective of the type of vascular intervention. RESULTS: One thousand one hundred fifty-one patients were included. Eighty-two percent had a toe Pressure <45 mm Hg and 49% had an Ankle Pressure <80 mm Hg. Eight hundred one patients (70%) underwent an angiography. Out of these, 63% had vascular intervention, either percutaneous transluminal angioplasty (PTA; 39%) or reconstructive surgery (24%). Nine percent of the patients had one or more complications after angiography. PTA was multisegmental in 46% and to the crural arteries in 46%. Reconstructive surgery was distal in 51%. Age (P < .001), renal function impairment (P = .005), congestive heart failure (P = .01), number and type of ulcer (P < .001), and severity of PVD (P = .003) affected the outcome of ulcers. PTA and reconstructive vascular surgery increased the probability of healing without amputation (odds ratio [OR], 1.77 and 2.05, respectively). CONCLUSION: Probability of ulcer healing is strongly related to comorbidity, extent of tissue involvement, and severity of PVD in patients with diabetes with severe PVD.
Dennis K Yue - One of the best experts on this subject based on the ideXlab platform.
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tbi or not tbi that is the question is it better to measure toe Pressure than Ankle Pressure in diabetic patients
Diabetic Medicine, 2001Co-Authors: Belinda Brooks, R Dean, S Patel, Lynda Molyneaux, Dennis K YueAbstract:Aims Measurement of Ankle blood Pressure is a simple method of assessing lower limb arterial blood supply. However, its use in diabetes has been questioned due to the presence of medial artery calcification. Measurement of toe blood Pressure has been advocated as an alternative but it is technically more difficult. The aim of this study was to obtain information to guide clinicians as to when Pressure measurements should be taken at the toe. Methods Ankle brachial index (ABI) and toe brachial index (TBI) were measured by Doppler ultrasound, or photoplethysmography on 174 subjects with diabetes and 53 control subjects. The Bland and Altman method, and the Cohen's method of measuring agreement between two tests were used to compare ABI with TBI. Results The mean differences between ABI and TBI in control and diabetic subjects are 0.40 ± 0.13 and 0.37 ± 0.15, respectively. Nearly all diabetic patients with an ABI < 1.3 have an ABI–TBI gradient falling within the normal range established from the non-diabetic cohort. In contrast, the majority of diabetic subjects with an ABI ≥ 1.3 have ABI–TBI differences outside this range. When patients are categorized according to ABI and TBI, there is also good agreement between the tests when ABI is low or normal (84% and 78% agreement, respectively), but not when ABI is elevated. Conclusion In the majority of patients with diabetes, assessment of TBI conveys no advantage over ABI in determining perfusion Pressure of the lower limbs. Only in those patients with overt calcification, which gives an ABI ≥ 1.3, are toe Pressure measurements superior. This guideline should simplify assessment and treatment of diabetic patients with disease of the lower limbs. Diabet. Med. 18, 528–532 (2001)
Johan Thorne - One of the best experts on this subject based on the ideXlab platform.
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early revascularization after admittance to a diabetic foot center affects the healing probability of ischemic foot ulcer in patients with diabetes
European Journal of Vascular and Endovascular Surgery, 2014Co-Authors: Targ Elgzyri, Johan Thorne, Karlfredrik Eriksson, Per Nyberg, Jan Larsson, Jan ApelqvistAbstract:WHAT THIS PAPER ADDS This is, to the author’s knowledge, the first study that examines the influence of time to revascularization on outcome of ischemic foot ulcers in patients with diabetes. This study observed consecutively presenting and prospectively followed patients with diabetes, foot ulcers, and severe PAD, treated and followed by a multidisciplinary foot team. Shorter time to revascularization and less tissue destruction positively affects the probability of healing over time of ischemic foot ulcer in patients with diabetes.The present study highlights the need to prioritize investigation and revascularization in patients with diabetes and peripheral ischemia to improve the outcome of foot ulcer. Objectives: There is limited information about whether time from recognition of decreased perfusion to revascularization affects the probability of healing in a patient with a diabetic foot ulcer. The aim of the present study was to examine whether time to revascularization after referral to a multidisciplinary foot center was related to the outcome of foot ulcers in patients with diabetes and severe peripheral arterial disease (PAD). Methods: Patients with diabetes, a foot ulcer, and a systolic toe Pressure <45 mmHg or an Ankle Pressure <80 mmHg were prospectively included at the foot center, and considered for revascularization according to a preset protocol. All patients underwent invasive revascularization, either percutaneous transluminal angioplasty (PTA) or reconstructive vascular surgery. All patients had continuous follow-up until healing or death irrespective of the type of revascularization. Results: A total of 478 patients were included (age 74 [range 66e80] years, 60% males), of whom 315 patients (66%) had PTA, and 163 (34%) had reconstructive surgery. Of the 478 patients, 217 (45%) healed primarily, 88 (19%) healed after a minor amputation, 76 (16%) healed after a major amputation and 92 patients (19%) died unhealed. The median time from inclusion in the study to revascularization was 8 weeks (3e18 weeks). Time to vascular intervention within 8 weeks (p < .001), maximum Wagner grade reached < 3( p < .001), absence of peripheral edema (p ¼ .033), and presence of intermittent claudication (p ¼ .001) were related to a higher probability of healing. Conclusions: Time to revascularization and extent of tissue damage were related to the probability of healing of ischemic foot ulcer in patients with diabetes over time. In the presence of a decreased perfusion in a patient with diabetes and a foot ulcer not only revascularization per se but also timing of revascularization is important for the possibility of healing without a major amputation.
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factors related to outcome of neuroischemic ischemic foot ulcer in diabetic patients
Journal of Vascular Surgery, 2011Co-Authors: Jan Apelqvist, Targ Elgzyri, Per Nyberg, Magnus Löndahl, Jan Larsson, Johan ThorneAbstract:OBJECTIVES: Peripheral vascular disease (PVD) is an important limiting factor for healing in neuroischemic or ischemic diabetic foot ulcer. The purpose of this study was to identify factors related to healing in patients with diabetes with foot ulcers and severe PVD. METHODS: Patients with diabetes with a foot ulcer, consecutively presenting at a multidisciplinary foot center with a systolic toe Pressure <45 mm Hg or an Ankle Pressure <80 mm Hg were prospectively included, followed according to a preset program, and with the exception of specified exclusions, subjected to angiography offered vascular intervention when applicable. All patients had continuous follow-up until healing or death irrespective of the type of vascular intervention. RESULTS: One thousand one hundred fifty-one patients were included. Eighty-two percent had a toe Pressure <45 mm Hg and 49% had an Ankle Pressure <80 mm Hg. Eight hundred one patients (70%) underwent an angiography. Out of these, 63% had vascular intervention, either percutaneous transluminal angioplasty (PTA; 39%) or reconstructive surgery (24%). Nine percent of the patients had one or more complications after angiography. PTA was multisegmental in 46% and to the crural arteries in 46%. Reconstructive surgery was distal in 51%. Age (P < .001), renal function impairment (P = .005), congestive heart failure (P = .01), number and type of ulcer (P < .001), and severity of PVD (P = .003) affected the outcome of ulcers. PTA and reconstructive vascular surgery increased the probability of healing without amputation (odds ratio [OR], 1.77 and 2.05, respectively). CONCLUSION: Probability of ulcer healing is strongly related to comorbidity, extent of tissue involvement, and severity of PVD in patients with diabetes with severe PVD.
Belinda Brooks - One of the best experts on this subject based on the ideXlab platform.
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tbi or not tbi that is the question is it better to measure toe Pressure than Ankle Pressure in diabetic patients
Diabetic Medicine, 2001Co-Authors: Belinda Brooks, R Dean, S Patel, Lynda Molyneaux, Dennis K YueAbstract:Aims Measurement of Ankle blood Pressure is a simple method of assessing lower limb arterial blood supply. However, its use in diabetes has been questioned due to the presence of medial artery calcification. Measurement of toe blood Pressure has been advocated as an alternative but it is technically more difficult. The aim of this study was to obtain information to guide clinicians as to when Pressure measurements should be taken at the toe. Methods Ankle brachial index (ABI) and toe brachial index (TBI) were measured by Doppler ultrasound, or photoplethysmography on 174 subjects with diabetes and 53 control subjects. The Bland and Altman method, and the Cohen's method of measuring agreement between two tests were used to compare ABI with TBI. Results The mean differences between ABI and TBI in control and diabetic subjects are 0.40 ± 0.13 and 0.37 ± 0.15, respectively. Nearly all diabetic patients with an ABI < 1.3 have an ABI–TBI gradient falling within the normal range established from the non-diabetic cohort. In contrast, the majority of diabetic subjects with an ABI ≥ 1.3 have ABI–TBI differences outside this range. When patients are categorized according to ABI and TBI, there is also good agreement between the tests when ABI is low or normal (84% and 78% agreement, respectively), but not when ABI is elevated. Conclusion In the majority of patients with diabetes, assessment of TBI conveys no advantage over ABI in determining perfusion Pressure of the lower limbs. Only in those patients with overt calcification, which gives an ABI ≥ 1.3, are toe Pressure measurements superior. This guideline should simplify assessment and treatment of diabetic patients with disease of the lower limbs. Diabet. Med. 18, 528–532 (2001)
Iris Baumgartner - One of the best experts on this subject based on the ideXlab platform.
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analysis of in pact deep trial on the association between changes in perfusion from pre to postrevascularization and clinical outcomes in critical limb ischemia
Catheterization and Cardiovascular Interventions, 2017Co-Authors: Tarek A Hammad, Thomas Zeller, Iris Baumgartner, Dierk Scheinert, Krishna J Rochasingh, Mehdi H ShishehborAbstract:Objectives To quantify changes in Ankle and toe Pressure from pre- to post-endovascular revascularization for critical limb ischemia (CLI) and examine their association with major adverse limb events (MALE). Background Despite societal guidelines recommendation of routine hemodynamic surveillance following revascularization, little is known about hemodynamic assessment in CLI. Methods Among the 358 patients with CLI from the international multicenter IN.PACT DEEP trial, Ankle and toe Pressures measurements were available at both baseline and after intervention in 270 and 44 patients, respectively. The change in Ankle and toe Pressures in response to endovascular revascularization and its association with 1-year MALE (target limb revascularization, amputation, or death) were examined using Kaplan–Meier curves and multivariable Cox proportional hazard analyses. Corresponding optimal cutoff points were also identified. Results The mean increase in Ankle and toe Pressures following revascularization was 33 and 13 mmHg, respectively. Patients with an improvement of Ankle Pressure >73 mmHg or toe Pressure >1 mmHg had similarly the lowest incidence of MALE (23%), while the highest rate of MALE (50%) was found in those whose toe Pressure failed to improve by at least 1 mmHg following intervention. In addition, an increase in Ankle Pressure >73 mmHg was numerically protective against MALE, and more importantly, an increase in toe Pressure of >1 mmHg provided statistically significant protection from MALE (adjusted HR = 0.15, 95% CI: 0.04–0.57, P = 0.005). Conclusions Improvements in toe Pressure post revascularization are incremental and rarely normalize. Toe Pressure, compared to Ankle Pressure, is more useful in CLI and predicts future MALE.
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an analysis of in pact deep randomized trial on the limitations of the societal guidelines recommended hemodynamic parameters to diagnose critical limb ischemia
Journal of Vascular Surgery, 2016Co-Authors: Mehdi H Shishehbor, Tarek A Hammad, Thomas Zeller, Iris Baumgartner, Dierk Scheinert, Krishna J RochasinghAbstract:Objective Recent small single-center data indicate that the current hemodynamic parameters used to diagnose critical limb ischemia are insensitive. We investigated the validity of the societal guidelines-recommended hemodynamic parameters against core laboratory-adjudicated angiographic data from the multicenter IN.PACT DEEP (RandomIzed AmPhirion DEEP DEB vs StAndard PTA for the treatment of below the knee Critical limb ischemia) Trial. Methods Of the 358 patients in the IN.PACT DEEP Trial to assess drug-eluting balloon vs standard balloon angioplasty for infrapopliteal disease, 237 had isolated infrapopliteal disease with an available Ankle-brachial index (ABI), and only 40 of the latter had available toe Pressure measurements. The associations between ABI, Ankle Pressure, and toe Pressure with tibial runoff, Rutherford category, and plantar arch were examined according to the cutoff points recommended by the societal guidelines. Abnormal tibial runoff was defined as severely stenotic (≥70%) or occluded and scored as one-, two-, or three-vessel disease. A stenotic or occluded plantar arch was considered abnormal. Results Only 14 of 237 patients (6%) had an ABI Conclusions The current recommended hemodynamic parameters fail to identify a significant portion of patients with lower extremity ulcers and angiographically proven severe disease. Toe Pressure has better sensitivity and should be considered in all patients with critical limb ischemia.
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effect of fibroblast growth factor nv1fgf on amputation and death a randomised placebo controlled trial of gene therapy in critical limb ischaemia
The Lancet, 2011Co-Authors: J J F Belch, Iris Baumgartner, Sigrid Nikol, William R Hiatt, Vickie I Driver, Lars Norgren, Eric Van BelleAbstract:Summary Background Patients with critical limb ischaemia have a high rate of amputation and mortality. We tested the hypothesis that non-viral 1 fibroblast growth factor (NV1FGF) would improve amputation-free survival. Methods In this phase 3 trial (EFC6145/TAMARIS), 525 patients with critical limb ischaemia unsuitable for revascularisation were enrolled from 171 sites in 30 countries. All had ischaemic ulcer in legs or minor skin gangrene and met haemodynamic criteria (Ankle Pressure Findings 259 patients were assigned to NV1FGF and 266 to placebo. All 525 patients were analysed. The mean age was 70 years (range 50–92), 365 (70%) were men, 280 (53%) had diabetes, and 248 (47%) had a history of coronary artery disease. The primary endpoint or components of the primary did not differ between treatment groups, with major amputation or death in 86 patients (33%) in the placebo group, and 96 (36%) in the active group (hazard ratio 1·11, 95% CI 0·83–1·49; p=0·48). No significant safety issues were recorded. Interpretation TAMARIS provided no evidence that NV1FGF is effective in reduction of amputation or death in patients with critical limb ischaemia. Thus, this group of patients remains a major therapeutic challenge for the clinician. Funding Sanofi-Aventis, Paris, France.
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effect of fibroblast growth factor nv1fgf on amputation and death a randomised placebo controlled trial of gene therapy in critical limb ischaemia
The Lancet, 2011Co-Authors: J J F Belch, Iris Baumgartner, Sigrid Nikol, William R Hiatt, Vickie I Driver, Lars Norgren, Eric Van BelleAbstract:Summary Background Patients with critical limb ischaemia have a high rate of amputation and mortality. We tested the hypothesis that non-viral 1 fibroblast growth factor (NV1FGF) would improve amputation-free survival. Methods In this phase 3 trial (EFC6145/TAMARIS), 525 patients with critical limb ischaemia unsuitable for revascularisation were enrolled from 171 sites in 30 countries. All had ischaemic ulcer in legs or minor skin gangrene and met haemodynamic criteria (Ankle Pressure Findings 259 patients were assigned to NV1FGF and 266 to placebo. All 525 patients were analysed. The mean age was 70 years (range 50–92), 365 (70%) were men, 280 (53%) had diabetes, and 248 (47%) had a history of coronary artery disease. The primary endpoint or components of the primary did not differ between treatment groups, with major amputation or death in 86 patients (33%) in the placebo group, and 96 (36%) in the active group (hazard ratio 1·11, 95% CI 0·83–1·49; p=0·48). No significant safety issues were recorded. Interpretation TAMARIS provided no evidence that NV1FGF is effective in reduction of amputation or death in patients with critical limb ischaemia. Thus, this group of patients remains a major therapeutic challenge for the clinician. Funding Sanofi-Aventis, Paris, France.