HEAL-IT Bauer Sumpio Yale University Suephy C. Chen, William S. Weintraub Emory University Sponsor: Otsuka America
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