HEAL-ITBauer Sumpio

Yale University

Suephy C. Chen, William S. Weintraub

Emory University

Sponsor: Otsuka America

Facts of The TrialWilliam S. Weintraub, MD

Professor of Medicine

Emory University

Director, Emory Center for Outcomes Research

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

Specific Aim:

To evaluate the ability of cilostazol (Pletal®) to

improve wound healing of ischemic foot ulcers in

combination with standard local wound care

compared to local wound care alone.

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

Background:• Foot ulcer prevalence- 1-2% in over-50 age group• PVD accounts for up to 2/3 of the etiology• Cilostazol originally utilized for healing ischemic

ulcers in Japan but only anecdotal reports• Cilostazol approved by FDA for claudication 1999

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

Hypothesis:

Cilostazol will improve wound healing in ischemic

leg ulcers in combination with standard local

wound care compared to local wound care alone.

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

Primary Endpoint:

Mean rate of healing of target ulcer

(% per month, where a month is 30 days)

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

Secondary Endpoints:

1) Change in target ulcer area (cm2)

2) Target ulcer completely healed (yes/no)

3) Time to complete healing of target ulcer

4) Percent healing of target ulcer

5) Number of ulcers on leg where target ulcer resides

6) Quality of life improvement

7) Cost

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

Design:

1) Multicenter, randomized double blind clinical trial

2) 300 patients at 20 sites (15-20 per site)

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

Study Drug Handling:

1) Be sure that patient number on study drug and patient number on CRF

match. Be sure to go in order, i.e. do not skip numbers.

2) Patients will be given a full 6-month supply of study drug in a kit containing

pill bottles and a daily dispenser

3) Study drug is in bottles containing 132 tablets.

4) At three month and six month visits patients should bring their kit and all

pill bottles, empty, partially full and full for pill count.

5) Patients be resupplied if they lose their original supply.

6) All remaining drug supplies should be returned to ECOR at the end of the

study

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

Follow-up:

1) Clinical follow-up every month

2) Place a dated, signed copy of follow-ups in the

medical record

3) Ulcer counts, target ulcer border tracing and digital

photographs will be done at each visit

4) Quality of life assessments done at baseline and at 6

months

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

Site monitoring:•All sites will be monitored via CRF & photos.•Sites will be asked for copies of source

documentation after the first 2 patients are

enrolled, or 1 month after initiation of the trial,

whichever occurs first.

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

Case Report Forms:

1) Case report forms is made up in Teleform

2) Copy pages and save copy.

3) Send originals to ECOR every month

4) FAX randomization form to ECOR at

randomization: 404-727-6495

5) FAX SAE forms to ECOR after event

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

Communications:

Reporting will include:

1) DCFs

2) Summary reporting

3) Newsletter

4) Website

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

HEAL-IT website:

http://www.emory.edu/WHSC/CARDIOLOGY/CVEC/HealIT

Login: healit

Password: woundhealing

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

Patient DemographicsVariable Mean (SD, N)

Age (years) 70 (13, 22)

Height (cm) 169.6 (19.8, 21)

Weight (kg) 81.2 (21.2, 21)

Toe Pressure (mmHg) 31.5 (7.3, 8)

Chest TCPO2 48.8 (8.8, 14)

Dorsum TCPO2 29.7 (7.0, 15)

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

Patient Demographics

Variable N (%)

Male Gender 16 (73)

Caucasian Race 17 (77)

Diabetes 15 (68)

Hypertension 14 (64)

Renal Insufficiency 3 (14)

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

Patient DemographicsVariable N (%)

Cardiac Disease 10 (45)

CABG 3 (30)

MI 7 (70)

PCI 3 (30)

CABG, MI, and PCI denotes those patients who had cardiac disease and CABG, MI, and/or PCI.

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

Patient Demographics

Variable N (%)

Cerebrovascular Disease 4 (18)

Prior Stroke 3 (75)

Prior Stroke denotes those patients with cerebrovascular disease who had a prior stroke.

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

Ulcer Location

Location N

Digit 12

MTP Joint 1

Mid-Plantar Arch 3

Metatarsal Head 4

Other Location 5

Multiple Locations are possible. Example: Metatarsal Head and Digit.

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

Ulcer Location

Location N (%)

Medial Aspect 13 (59)

Right Side 11 (50)

1+ Edema 4 (19)

Number of Ulcers

1

2

3

13 (59)

8 (36)

1 (5)

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

So where are we?

23 patients randomized

Sample size 300

We are 8% of the way there

To finish enrollment by end of

October we need 21 a week

Or about one patient per site per week

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

Can we have a meaningful trial

with fewer patients?

Yes (so don’t give up)

However, the more patients we

randomize, the stronger the study

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

Why this trial is important:

Arterial ulcers are a serious problem

in patients with PVD

Anecdotal evidence support the use of

Pletal for wound healing

Pletal will not become routine for

wound healing without this trial

If positive, HEAL-IT will offer

patients a beneficial new therapy

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial

What do we need to do?

Randomize, Randomize, Randomize

HEAL-ITHEALing of

Ischemic Foot Ulcers With

Cilostazol Trial