HELP-Apheresis in Diabetic Ischemic Foot Treatment (H.A.D.I.F)

NCT01518205 | Completed

• 1 other identifier: MZenti HADIF
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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. 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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Secondary Outcomes (6)

• Improvement of the peripheral oxygenation evaluated by means of transcutaneous oximetry measurement at foot level: TcP O2 (mmHg).

  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)

  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)

  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).

  12 months

• proportion of subjects with minor amputation (only toe or part of the foot removed)- in agreement with the approved amendment

  12 months

Study Arms (2)

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.

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.

Interventions

LDL-apheresis DEVICE

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.

Also known as: H.E.L.P. apheresis, TT: traditional therapy

LDL-apheresis and TT

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Universita di Verona: lead

Study Sites (1)

universita Verona

Verona, Verona, 37100, Italy

Location

MeSH Terms

Conditions

Foot Ulcer; Arteriosclerosis Obliterans; Diabetes Mellitus; Diabetic Foot; Peripheral Arterial Disease; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Foot Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Leg Ulcer; Skin Ulcer; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetic Neuropathies; Atherosclerosis; Peripheral Vascular Diseases

Study Officials

• Maria Grazia Zenti, MD

  Division of Endocrinology and Metabolic Diseases, University Hospital of Verona

  PRINCIPAL INVESTIGATOR

• Enzo Bonora, MD, PhD

  Division of Endocrinology and Metabolic Diseases, University Hospital of Verona

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Maria Grazia Zenti,MD, Division of Endocrinology and Metabolic Diseases, University Hospital of Verona

Study Record Dates

• First Submitted: January 22, 2012
• First Posted: January 25, 2012
• Study Start: February 1, 2012
• Primary Completion: September 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 4, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)