Foot UlcersHADIFNCT01518205
HELP-Apheresis in Diabetic Ischemic Foot Treatment (H.A.D.I.F)
A study testing LDL-apheresis in people with Foot Ulcers and Arteriosclerosis Obliterans, run by Universita di Verona at 1 site in Italy.
Trial summary
Diabetic foot (DF) is a common, severe and costly complication of diabetes. DF is underlied by neuropathy, atherosclerosis of distal arteries and infection, which result in tissue ulcers and necrosis. Alterations in microcirculatory function and in blood rheology may concur in causing tissue damage. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Foot Ulcers, Arteriosclerosis Obliterans, Diabetes Mellitus
- What is being tested?
- LDL-apheresis
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteItaly
- Study dates
- Feb 2012to Dec 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diabetic patients
- Ischemic diabetic ulcers (class I, II and III Texas Wound Classification System);
- documented peripheral vasculopathy with at least a previous event of failed revascularization (no ulcer healing).
Who cannot join
- Patient refusal to participate
- BMI > 35 kg/m2
- Ischemic diabetic ulcers class III Texas Wound Classification System
- Patients presenting a bleeding diathesis, malignant tumor, heart failure not allowing extracorporeal technique.
- Haemodialysis
Trial locations and contacts
1 site in 1 country.
About this study
Official title: HELP-Apheresis in Diabetic Ischemic Foot Treatment (H.A.D.I.F): a RCTrial to Evaluate the Effect of LDL-apheresis on the Recovery of Diabetic Ulcers in Patients With Peripheral Vasculopathy Not Susceptible to Revascularization.
Diabetic foot (DF) is a common, severe and costly complication of diabetes. DF is underlied by neuropathy, atherosclerosis of distal arteries and infection, which result in tissue ulcers and necrosis. Alterations in microcirculatory function and in blood rheology may concur in causing tissue damage.
In recent years there has been accumulating evidence that LDL apheresis (LA) does not only reduce cholesterol but also has a series of pleiotropic effects that improve the microcirculation, increasing peripheral tissue perfusion.
Read more
HADIF is a randomized, multicentric, prospective clinical study aimed at assessing the effect of LDL apheresis treatment in association with traditional therapy for ulcers, in patients with an ischemic diabetic foot ulcer (class I and II Texas Wound Classification System)and peripheral vasculopathy not susceptible to revascularization. A total of 132 patients will be enrolled. Participants will be centrally randomized to receive traditional therapy alone (TT) or in association with LA. TT includes standard medication of ulcers, antiaggregant therapy and statins. LA will be performed with HELP system, for a total of 10 sessions in 9 weeks. The primary end-point of the study is ulcer healing; secondary endpoints include improvements of peripheral oxygenation, resolution of pain, reduction of circulating inflammatory markers, cardiovascular events during one year's follow-up.
This clinical Study has been approved by local EC on 25 may 2011 (Study number 1953).
TO BE NOTED: since diabetic patients in our "Diabetic-Foot UNIT" often presented foot ulcers more severe than class II Texas, a formal amendment has been submitted to EC for recruiting patients with diabetic foot ulcer of class III Texas. The amendment was already approved on 5 may 2012.
Read the detailed description
Aim of the protocol is to evaluate the effect of LDL-apheresis in combination with traditional therapy, on the recovery of diabetic ulcers in patients suffering from diabetic ischemic foot and peripheral vasculopathy that cannot be revascularized.
Patients who qualify for the study will be randomized to the traditional treatment combined to apheresis (Experimental Arm) or to the standard treatment only (control Arm).
The randomization stratified according to the lesion gravity level (class TEXAS I vs II vs III),allocation 1:1. The randomization list will be generated by the statistic software "Stata 11". The lists of randomization (one list for each class TEXAS ) will be generated and will be stored by the coordinator centre. When a patient satisfies the study inclusion criteria, will be contacted the coordinator centre (by phone/mail) for group allocation.
132 patients will be enrolled (66 patients in experimental arm, 66 patients in control arm).
Traditional Therapy (TT) includes standard medication of ulcers, antiaggregant therapy and statins.
LDL-apheresis (intervention Arm) will be performed with HELP system, for 10 session in 9 weeks.
Blood samples will be collected (at basal, and after 3-6-9-12 months) in order to determine the following parameters: glycaemia, insulin, glycated haemoglobin, microalbuminuria/creatinuria,CBC, fibrinogen, total cholesterol, HDL-cholesterol, LDL-cholesterol, Triglycerides, Lp(a), C-reactive protein (CRP), pentraxin3 (PTX3).
Furthermore, in patients of experimental arm, blood samples will be collected at basal and at the end of LDL-apheresis sessions no. 2 and 10 in order to determine CBC, fibrinogen, total cholesterol, HDL-cholesterol, LDL-cholesterol, Triglycerides, Lp(a), CRP, PTX3 (time schedule, after 1 and 9 weeks).
The value of the lab tests obtained at the end of apheresis will be normalized due to a possible hemodilution, according to the following formula:
F dil= (1 - Htc pre-apheresis) / ( 1 - Htc post-apheresis). Xcorrect = Xmeasured * Fdil.
Ulcer evaluation: staging according to Texas Wound classification System and ulcer surface evaluation (diameter, mapping of the lesions by means of drawing their profiles on Opsite film; digital picture): at basal, at 9th week and after a 3-6-9-12 month follow-up.
The ulcers evolution will be "in blind" monitored by an evaluator who will check ulcer-map and digital picture without knowing to which randomization arm they belong.
Transcutaneous oximetry: basal, at 4th week (i.e. after the 5th apheretic session). at 9th week (at the end of the 10 apheresis sessions) and after the next 3-6-9-12 month follow-up.
Questionnaire on quality of life (SF36): basal, at 9th week (at the end of the 10 apheresis sessions) and after the next 6-12 month follow-up.
Pain intensity rate (verbal numeric range) basal, at 9th week (at the end of the 10 apheresis sessions) and after the next 3-6-9-12 month follow-up.
Doppler flowmeter : basal, at 9th week (at the end of the 10 apheresis sessions) and in the subsequent follow-up at 6 and 12 months.
- Conditions
- Foot Ulcers, Arteriosclerosis Obliterans, Diabetes Mellitus
- Being tested
- LDL-apheresis
- Keywords
- diabetic foot ulcers,, peripheral arterial disease,, heparin-induced extracorporal lipid apheresis., inflammatory markers, type 2 diabetes, LDL-cholesterol
- Medical subject headings
- Foot Ulcer, Arteriosclerosis Obliterans, Diabetes Mellitus, Diabetic Foot, Peripheral Arterial Disease, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LDL-apheresisDevice
Also called H.E.L.P. apheresis, TT: traditional therapy
The patient of the Arm "LDL-apheresis" in addition to standard therapy, will undergo a cycle of LDL-apheresis.
LDL-apheresis will be performed with B.Braun Avitum H.E.L.P. System. Apheretic treatment scheme: 10 apheretic sessions carried out as follows: the first 2 with a 3 day distance (i.e. 2 treatments in one week), successively 1 session per week (every 7 days).
To perform the treatment, the forearm surface veins will be punctured by means of 17 Ga needles, as an alternative a two-ways CVC will be used.
| Study group | Role | What they receive |
|---|---|---|
| LDL-apheresis and TT | Experimental | The patient of the experimental Arm, in addition to Traditional Therapy (TT), will undergo a cycle of 10 LDL-apheresis session.
Apheretic treatment scheme: 10 apheretic session carried out as follow: first and second apheresis with a 3 days interval (i.e. 2 treatment in one week), then one session per week (every 7 days).
To perform the treatment, the forearm surface veins will be punctured by means of 17 Ga needles, as an alternative a two-ways CVC will be used. Receives: Device: LDL-apheresis |
| Traditional Treatment | No intervention | All patients will receive the traditional treatment for the ulcer healing Standardized medication. All lesions taken into consideration will be treated in a standardized way, with a different approach according to the presence of a possible infection. The evolution of lesions might be documented by means of mapping the same by drawing their profiles on an Opsite film. antibiotics therapy (according to antibiogram). Anti-platelet therapy. Statin therapy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects obtaining the ulcer healing (Class 0A according to TEXAS classification) after 12 month from the study starts.
Ulcer evaluation: staging according to Texas Wound classification System and ulcer evaluation (surface diameter, mapping of the lesions by means of drawing their profiles on Opsite film,and digital picture), at basal, at 9th week and after a 3-6-9-12 month follow-up.
Measured: 12 months
Secondary outcomes (6)
Improvement of the peripheral oxygenation evaluated by means of transcutaneous oximetry measurement at foot level: TcP O2 (mmHg).
Measured: basal, at 4th and 9th week and after 3-6-9-12 month follow-up
Evaluation of pain level variation (verbal numeric range; score from 1 to 10)
Measured: basal, at 4th and 9th week and after 3-6-9-12 month follow-up
Lowering of circulating inflammation markers (C Reactive Protein, Fibrinogen). CRP plasmatic concentration (mg/L) and fibrinogen (g/L)
Measured: at the beginning of the study and respectively after 3 - 6 - 9 e 12 months.
Rate of cardiovascular events in the observation period (1-year follow-up).
Measured: 12 months
proportion of subjects with minor amputation (only toe or part of the foot removed)- in agreement with the approved amendment
Measured: 12 months
proportion of subjects with major amputation (these are usually below the knee or above the knee)- in agreement with the approved amendment
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2012 (estimated)
- Study startFeb 2012
- Primary completionSep 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Foot UlcersStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universita di Verona
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Maria Grazia Zenti, Universita di Verona
- Investigators
- Maria Grazia Zenti, MD, Principal investigator, Division of Endocrinology and Metabolic Diseases, University Hospital of VeronaEnzo Bonora, MD, PhD, Study director, Division of Endocrinology and Metabolic Diseases, University Hospital of Verona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01518205
- Sponsor's protocol ID
- MZenti HADIF
- Acronym
- HADIF
- Status last verified
- Jan 2017
- First submitted
- 22 Jan 2012
- Last updated
- 4 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HELP-Apheresis in Diabetic Ischemic Foot Treatment (H.A.D.I.F): a RCTrial to Evaluate the Effect of LDL-apheresis on the Recovery of Diabetic Ulcers in Patients With Peripheral Vasculopathy Not Susceptible to Revascularization.
- ClinicalTrials.gov ID
- NCT01518205
- Acronym / sponsor ID
- HADIF / MZenti HADIF
- Conditions
- Foot Ulcers, Arteriosclerosis Obliterans, Diabetes Mellitus
- Keywords
- diabetic foot ulcers,, peripheral arterial disease,, heparin-induced extracorporal lipid apheresis., inflammatory markers, type 2 diabetes, LDL-cholesterol
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Universita di VeronaUniversity, hospital or other
- Study start
- Feb 2012
- Primary completion
- Sep 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 25 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Diabetic foot (DF) is a common, severe and costly complication of diabetes. DF is underlied by neuropathy, atherosclerosis of distal arteries and infection, which result in tissue ulcers and necrosis. Alterations in microcirculatory function and in blood rheology may concur in causing tissue damage.
In recent years there has been accumulating evidence that LDL apheresis (LA) does not only reduce cholesterol but also has a series of pleiotropic effects that improve the microcirculation, increasing peripheral tissue perfusion.
HADIF is a randomized, multicentric, prospective clinical study aimed at assessing the effect of LDL apheresis treatment in association with traditional therapy for ulcers, in patients with an ischemic diabetic foot ulcer (class I and II Texas Wound Classification System)and peripheral vasculopathy not susceptible to revascularization. A total of 132 patients will be enrolled. Participants will be centrally randomized to receive traditional therapy alone (TT) or in association with LA. TT includes standard medication of ulcers, antiaggregant therapy and statins. LA will be performed with HELP system, for a total of 10 sessions in 9 weeks. The primary end-point of the study is ulcer healing; secondary endpoints include improvements of peripheral oxygenation, resolution of pain, reduction of circulating inflammatory markers, cardiovascular events during one year's follow-up.
This clinical Study has been approved by local EC on 25 may 2011 (Study number 1953).
TO BE NOTED: since diabetic patients in our "Diabetic-Foot UNIT" often presented foot ulcers more severe than class II Texas, a formal amendment has been submitted to EC for recruiting patients with diabetic foot ulcer of class III Texas. The amendment was already approved on 5 may 2012.
Detailed description
Aim of the protocol is to evaluate the effect of LDL-apheresis in combination with traditional therapy, on the recovery of diabetic ulcers in patients suffering from diabetic ischemic foot and peripheral vasculopathy that cannot be revascularized.
Patients who qualify for the study will be randomized to the traditional treatment combined to apheresis (Experimental Arm) or to the standard treatment only (control Arm).
The randomization stratified according to the lesion gravity level (class TEXAS I vs II vs III),allocation 1:1. The randomization list will be generated by the statistic software "Stata 11". The lists of randomization (one list for each class TEXAS ) will be generated and will be stored by the coordinator centre. When a patient satisfies the study inclusion criteria, will be contacted the coordinator centre (by phone/mail) for group allocation.
132 patients will be enrolled (66 patients in experimental arm, 66 patients in control arm).
Traditional Therapy (TT) includes standard medication of ulcers, antiaggregant therapy and statins.
LDL-apheresis (intervention Arm) will be performed with HELP system, for 10 session in 9 weeks.
Blood samples will be collected (at basal, and after 3-6-9-12 months) in order to determine the following parameters: glycaemia, insulin, glycated haemoglobin, microalbuminuria/creatinuria,CBC, fibrinogen, total cholesterol, HDL-cholesterol, LDL-cholesterol, Triglycerides, Lp(a), C-reactive protein (CRP), pentraxin3 (PTX3).
Furthermore, in patients of experimental arm, blood samples will be collected at basal and at the end of LDL-apheresis sessions no. 2 and 10 in order to determine CBC, fibrinogen, total cholesterol, HDL-cholesterol, LDL-cholesterol, Triglycerides, Lp(a), CRP, PTX3 (time schedule, after 1 and 9 weeks).
The value of the lab tests obtained at the end of apheresis will be normalized due to a possible hemodilution, according to the following formula:
F dil= (1 - Htc pre-apheresis) / ( 1 - Htc post-apheresis). Xcorrect = Xmeasured * Fdil.
Ulcer evaluation: staging according to Texas Wound classification System and ulcer surface evaluation (diameter, mapping of the lesions by means of drawing their profiles on Opsite film; digital picture): at basal, at 9th week and after a 3-6-9-12 month follow-up.
The ulcers evolution will be "in blind" monitored by an evaluator who will check ulcer-map and digital picture without knowing to which randomization arm they belong.
Transcutaneous oximetry: basal, at 4th week (i.e. after the 5th apheretic session). at 9th week (at the end of the 10 apheresis sessions) and after the next 3-6-9-12 month follow-up.
Questionnaire on quality of life (SF36): basal, at 9th week (at the end of the 10 apheresis sessions) and after the next 6-12 month follow-up.
Pain intensity rate (verbal numeric range) basal, at 9th week (at the end of the 10 apheresis sessions) and after the next 3-6-9-12 month follow-up.
Doppler flowmeter : basal, at 9th week (at the end of the 10 apheresis sessions) and in the subsequent follow-up at 6 and 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LDL-apheresis and TT | Experimental | Device: LDL-apheresisThe patient of the experimental Arm, in addition to Traditional Therapy (TT), will undergo a cycle of 10 LDL-apheresis session. Apheretic treatment scheme: 10 apheretic session carried out as follow: first and second apheresis with a 3 days interval (i.e. 2 treatment in one week), then one session per week (every 7 days). To perform the treatment, the forearm surface veins will be punctured by means of 17 Ga needles, as an alternative a two-ways CVC will be used. |
| Traditional Treatment | No intervention | –All patients will receive the traditional treatment for the ulcer healing Standardized medication. All lesions taken into consideration will be treated in a standardized way, with a different approach according to the presence of a possible infection. The evolution of lesions might be documented by means of mapping the same by drawing their profiles on an Opsite film. antibiotics therapy (according to antibiogram). Anti-platelet therapy. Statin therapy. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diabetic patients
- Ischemic diabetic ulcers (class I, II and III Texas Wound Classification System);
- documented peripheral vasculopathy with at least a previous event of failed revascularization (no ulcer healing).
Key exclusion criteria (5 listed)
- Patient refusal to participate
- BMI > 35 kg/m2
- Ischemic diabetic ulcers class III Texas Wound Classification System
- Patients presenting a bleeding diathesis, malignant tumor, heart failure not allowing extracorporeal technique.
- Haemodialysis
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 |
|---|---|---|
| LDL-apheresisAlso: H.E.L.P. apheresis, TT: traditional therapyThe patient of the Arm "LDL-apheresis" in addition to standard therapy, will undergo a cycle of LDL-apheresis. LDL-apheresis will be performed with B.Braun Avitum H.E.L.P. System. Apheretic treatment scheme: 10 apheretic sessions carried out as follows: the first 2 with a 3 day distance (i.e. 2 treatments in one week), successively 1 session per week (every 7 days). To perform the treatment, the forearm surface veins will be punctured by means of 17 Ga needles, as an alternative a two-ways CVC will be used. | Device | LDL-apheresis and TT |
Primary outcome
Proportion of subjects obtaining the ulcer healing (Class 0A according to TEXAS classification) after 12 month from the study starts.
Time frame: 12 months
Ulcer evaluation: staging according to Texas Wound classification System and ulcer evaluation (surface diameter, mapping of the lesions by means of drawing their profiles on Opsite film,and digital picture), at basal, at 9th week and after a 3-6-9-12 month follow-up.
6 secondary outcomes
Improvement of the peripheral oxygenation evaluated by means of transcutaneous oximetry measurement at foot level: TcP O2 (mmHg).
Time frame: basal, at 4th and 9th week and after 3-6-9-12 month follow-up
Evaluation of pain level variation (verbal numeric range; score from 1 to 10)
Time frame: basal, at 4th and 9th week and after 3-6-9-12 month follow-up
Lowering of circulating inflammation markers (C Reactive Protein, Fibrinogen). CRP plasmatic concentration (mg/L) and fibrinogen (g/L)
Time frame: at the beginning of the study and respectively after 3 - 6 - 9 e 12 months.
Rate of cardiovascular events in the observation period (1-year follow-up).
Time frame: 12 months
proportion of subjects with minor amputation (only toe or part of the foot removed)- in agreement with the approved amendment
Time frame: 12 months
proportion of subjects with major amputation (these are usually below the knee or above the knee)- in agreement with the approved amendment
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2017.
- Individual participant dataSharing planned: No
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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.
Maria Grazia Zenti, MD principal investigator
Division of Endocrinology and Metabolic Diseases, University Hospital of Verona
Enzo Bonora, MD, PhD study director
Division of Endocrinology and Metabolic Diseases, University Hospital of Verona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing LDL-apheresis in people with Foot Ulcers and Arteriosclerosis Obliterans, run by Universita di Verona at 1 site in Italy.
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 3 inclusion and 5 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 4 Jan 2017. 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 Italy. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Proportion of subjects obtaining the ulcer healing (Class 0A according to TEXAS classification) after 12 month from the study starts. (time frame: 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 4 Jan 2017.