Safety and Efficacy Study of APIC-PRP in Non-healing Diabetic Foot Ulcers

A Multi-Center, Randomized Trial Comparing the Effectiveness of APIC-PRP to Control, When Added to Standard of Care in the Treatment of Non-healing Diabetic Foot Ulcers

Patients have a diabetic foot ulcer that is older than 4 weeks and has been treated with physician-selected standard of care treatment such as debridement, hydrogel or saline irrigation, primary dressing, and offloading will be randomized into one of two groups, the Standard of Care (SoC) or APIC-PRP + SoC. APIC-PRP has high level of platelets that produce growth factors that can help in wound healing.

Study Overview

• Status: Unknown
• Conditions: Diabetic Foot Ulcer
• Intervention / Treatment: Device: APIC-PRP; Other: Placebo, Saline plus standard of care

• Study Type: Interventional
• Enrollment (Anticipated): 274
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Prior to the first clinical intervention, a signed Informed Consent Form (ICF) and Data Consent Form (DCF) must be obtained from the subject or legal representative
• Diagnosed with insulin-dependent or non-insulin-dependent diabetes (Type I or II, respectively), requiring medical treatment as determined by the physician
• Subjects will have only one diabetic foot ulcer on the target limb (referred to as the Index Ulcer)
• The Index Ulcer, classified using the University of Texas Wound Classification System (Appendix 7), is located on the dorsal, plantar, medial, or lateral aspect of the foot or heel (including all toe surfaces)
• Debrided ulcer size between 1 cm2 and 4 cm2. See Appendix 3 for instructions on wound area measurement
• DFU with a duration ≥ 1 month at first visit
• The target ulcer is free of clinical signs of infection, identified by inflammation (redness, warmth, swelling, tenderness, or pain) or purulent exudates (Lipsky et al, 2012).
• The patient meets Medicare/Medicaid eligibility requirements. Subject's ulcer extends through the dermis and into subcutaneous tissue (granulation tissue may be present) but without exposure of muscle, tendon, bone or joint capsule.
• Post-debridement, subject's wound is free of necrotic debris and appears to be made up of healthy vascularized tissue.
• Demonstrated adequate offloading regimen.
• Subject has adequate circulation to the study foot as evidenced by a Doppler measured ankle-bronchial index (ABI) of ≥ 0.7 after 10 minutes of rest
• Age >18 years old at the time the informed consent is signed
• Female subjects must have a negative urine pregnancy test prior to the first treatment
• Subject must be willing to comply with the Protocol, which will be assessed by enrolling clinician

Exclusion Criteria:

• Subject has inadequate venous access the blood draw required for APIC-PRP Administration. Subjects with PIC or IV access are preferred.
• Hemoglobin of less than 12 g/dL
• Inadequate amount of blood drawn to produce sufficient APIC-PRP. One complete APIC-PRP preparation requires 114ml of blood drawn per APIC-PRP preparation.
• Subject's ulcer has increased in size by >50% during the run-in Screening period.
• If the subject's ulcer healed by 25% or more during the run-in Screening period they will be excluded.
• Presence of another wound that is concurrently treated and might interfere with treatment of the index wound by APIC-PRP (malignancy in nearby wound)
• Ulcer not of DFU pathophysiology (e.g., venous, vasculitic, radiation, rheumatoid, collagen vascular disease, pressure, or arterial etiology)
• The target ulcer demonstrates underlying osteomyelitis, defined as infection in the bone, identified by Fever, chills, or pain in the infected bone. Any exposed bone will be classified as osteomyelitis.
• Subject has a history of bleeding disorder.
• Any malignancy other than non-melanoma skin cancer requiring treatment with immunosuppressive or chemotherapeutic agents, radiotherapy or corticosteroids less than 30 days before enrolment.
• Subject has gangrene present on any part of the affected limb. Subject's ulcer is over a Charcot deformity of the mid-foot ("Rocker-Bottom Foot") or over the tarsal bones-talus, distal calcaneus, navicular, and cuboid.
• Subject's ulcer has tunnels or sinus tracts that cannot be completely debrided.
• Subject has severe malnutrition as evidenced by albumin < 2.5 g/dL. A previous serum albumin test that is <6 weeks old is sufficient for this criteria.
• Subject has Acquired Immunodeficiency Syndrome (AIDS), liver disease, aplastic anemia, scleroderma, malignancy, cellulitis, suspected osteomyelitis or other evidence of systemic infection, or is Human Immunodeficiency Virus (HIV)-positive.
• Subject has any elective osseous procedures to the study foot within 30 days prior to the Initial Visit.
• Subject is on dialysis.
• Subjects who are cognitively impaired and therefore can not give consent, and do not have a healthcare proxy
• Subjects who, in the opinion of the Investigator, represent poor medical, psychological or psychiatric risks for whom therapy with an investigational product would be unwise.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: APIC-PRP and Standard of Care; APIC-PRP	Device: APIC-PRP; APIC-PRP
Placebo Comparator: Placebo, Saline plus standard of care	Other: Placebo, Saline plus standard of care; Placebo, Saline plus standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete wound closure within 12 weeks	The primary outcome expected for this study is an increase in the proportion of DFUs that have exhibited complete closure within 12 weeks between the APIC-PRP + SoC groups and SoC alone groups.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in wound healing trajectory within 12 weeks	The secondary outcome expected for this study is an improvement in wound healing trajectory of DFUs over the 12 weeks treatment period between the APIC-PRP + SoC groups and SoC alone groups.	12 weeks
Improvement in wound healing for the patient to return to function over the 12 weeks	The secondary outcome expected for this study is an improvement in wound healing for the patient to return to function over the 12 weeks treatment period between the APIC-PRP + SoC groups and SoC alone groups.	12 weeks

Collaborators and Investigators

• Sponsor: Cytonics Corporation
• Investigators: Study Director: Gaetano J Scuderi, MD, Cytonics Corporation

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Anticipated): October 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: August 4, 2014
• First Submitted That Met QC Criteria: August 4, 2014
• First Posted (Estimate): August 6, 2014

Study Record Updates

• Last Update Posted (Estimate): August 6, 2014
• Last Update Submitted That Met QC Criteria: August 4, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Diabetic foot ulcer; Chronic Wounds; APIC-PRP
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Diabetic Foot; Foot Ulcer; Ulcer
• Other Study ID Numbers: Cyt201-01