Healing of Ischemic Leg Ulcers in Patients Treated With iSONIAzid

Study Overview
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Brief Summary
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The main objective of this trial is to study the healing effect of an oral drug (isoniazid) in patients with ischemic (arterial) leg ulcers defined by a systolic toe pressure <40 mm Hg.

Detailed Description
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Treatment of arterial ulcers is problematic. Previous pharmaceutical interventions with for example prostaglandins have produced only limited beneficial effects but have been associated with frequent adverse effects. Positive effects of isoniazid have been observed in a preclinical model of ischemic wound healing (Weinreich et al. Surgery 2010).

Official Title
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Healing of Ischemic Leg Ulcers: A Pilot Trial

Conditions
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Arterial Leg Ulcer

Intervention / Treatment
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* Drug: Isoniazid 300 milligram
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with ischemic leg ulcers unsuitable for vascular surgical intervention Systolic toe pressure < 40 mm Hg Ulcer duration > 3 months Ulcer area: 1-20 cm2 Written informed consent Exclusion Criteria: B-Hb < 6 mmol/l Aspartate transaminase > 50 U/l Diabetes mellitus > 10%HbA1c Usage of more than 10 mg prednisolone daily within the last 30 days Usage of cytotoxic agents with the last 3 months Usage of rifampicin, phenytoin, carbamazepin, theophylline, benzodiazepines (diazepam, triazolam), stavudine and/or valproat Alcohol abuse Hereditary galactose intolerance Hypersensitive to isoniazid or for one or more of the filling substances (magnesium stearate, povidone, talcum, lactose and starch) Cellulitis or deep infection (osteomyelitis and/or tendonitis) related to the ulcer Gangrene Participation in clinical trials within the last 7 days Pregnancy or breastfeeding Women of child bearing potential who decline to use contraception

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: A<br>Placebo tablets. | Drug: Placebo<br>* Placebo<br>|
| Experimental: B<br> | Drug: Isoniazid 300 milligram<br>* Tablets 150 milligram b.i.d.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage change of ulcer area 8 weeks after initiation of therapy. | The wound area is measured at week 0 (A0) and at 8 weeks (A8). From these measurements, the percentage (%) change of the wound area in relation to the start time (week 0) is determined from the following formula: (A0-A8)/A0*100. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain is evaluated by visual analogue scale (VAS). | The visual analogue scale ranges from 0 mm (minimum) to 100 mm (maximum), where the lower value the better is the outcome. | 8 weeks | 
| Occurrence of suspected unexpected serious adverse reactions (SUSAR) and serious adverse events (SAE) | the number of SUSAR and SAE occurring over the 8-week treatment period is recorded. | 8 weeks |