Transcript Startup slides - HEALing

HEAL-IT
Bauer Sumpio
Yale University
Suephy C. Chen, William S. Weintraub
Emory University
Sponsor: Otsuka America
HEAL-IT
HEALing 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-IT
HEALing 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-IT
HEALing 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-IT
HEALing 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-IT
HEALing 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-IT
HEALing of
Ischemic Foot
Ulcers With
Cilostazol Trial
Inclusion Criteria:
1) Non-healing ulcer of the foot (ankle forward)
2) Largest (target) ulcer on either foot is > 4 weeks and < 52 weeks old.
3) Target ulcer is full-thickness but does not involve bone.
4) Target ulcer is > 0.25 cm2 and < 12 cm2. Non-target ulcers do not have to
fulfill these criteria.
5) Transcutaneous oximetry (TcPO2) and/or toe pressures between 20 to 40
mm Hg
6) Age >18 years
7) Women of child-bearing potential: negative pregnancy and commitment to
remain abstinent or use contraception for the duration of the study.
HEAL-IT
HEALing of
Ischemic Foot
Exclusion Criteria:
Ulcers With
1. Venous stasis ulcers on foot with target ulcer
Cilostazol Trial
2. Lower extremity arterial revascularization (either bypass surgery or
angioplasty) less than 6 weeks prior to screening in leg with target ulcer
3. Charcot feet
4. More than 1+ pitting edema of the leg with the target ulcer
5. Patient has exposed bone and/or osteomyelitis in the leg with the target
ulcer
6. Patient is receiving radiation, chemotherapy, corticosteroids or immune
system suppressants
7. History of congestive heart failure of any severity
8. Known thrombocytopenia
9. Known bleeding diathesis
10. Known intolerance or hypersensitivity to cilostazol or any of the
ingredients of Pletal®
Cont’d
HEAL-IT
Exclusion Criteria cont’d:
11.
12.
13.
14.
15.
16.
17.
18.
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20.
HEALing of
Ischemic Foot
Ulcers With
Cilostazol Trial
Active peptic ulcer disease or GI bleeding
Known moderate or severe hepatic dysfunction
Current participation in another clinical trial
Major life-threatening illness or prognosis of less than 1 year
Inability to give informed consent
Concurrent use of pentoxifylline
Concurrent use of ticlopidine
Concurrent use of hyperbaric oxygen
Concurrent use of arginine
Use of Pletal® within 6 months of the trial.
HEAL-IT
HEALing 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-IT
HEALing of
Ischemic Foot
Ulcers With
Randomization and Initiation:
Cilostazol Trial
1) Decide if patient requires eschar debridement and treatment of infection
2) Informed consent after standard wound care.
3) Choose target ulcer
4) Tracing of target ulcer border and digital image of target ulcer
5) Send tracing to ECOR
6) Send image to both ECOR and Yale
7) Patient randomized to cilostazol vs placebo
8) Take 2 tablets twice a day, one table twice a day if on concomitant
administration of a drug interfering with cytochrome P-450 metabolism
(see appendix of protocol)
9) Continue study drug for 6 months
HEAL-IT
HEALing 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 loose their original supply.
6) All remaining drug supplies should be returned to ECOR at the end of the
study
HEAL-IT
HEALing 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-IT
HEALing of
Ischemic Foot
Ulcers With
Cilostazol Trial
Data Collection:
See table, page 6 of protocol
HEAL-IT
HEALing 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.
•All records will be reviewed.
HEAL-IT
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 screening forms to ECOR at
randomization: 404-727-6495
5) FAX SAE forms to ECOR after event
HEALing of
Ischemic Foot
Ulcers With
Cilostazol Trial
HEAL-IT
HEALing of
Ischemic Foot
Ulcers With
Cilostazol Trial
Target Ulcer Border Tracings and Images
1) Target ulcer border tracings –copy original and save
copy at site
2) Send original tracings to ECOR
3) Digital images – send copy (JPG file) to Yale and
ECOR. Save a copy.
4) Labels are provided
5) Send Tracings and Images every month
HEAL-IT
HEALing of
Ischemic Foot
Ulcers With
Cilostazol Trial
Communications:
Reporting will include:
1) DCFs
2) Summary reporting
3) Newsletter
HEAL-IT
HEALing of
Ischemic Foot
Ulcers With
Cilostazol Trial
ECOR Contact:
Felicia Warren, HEAL-IT Coordinator
1256 Briarcliff Road, Suite 1N
Atlanta, GA 30306
404-727-3683
HEAL-IT
HEALing of
Ischemic Foot
Ulcers With
Cilostazol Trial
Who to call:
Bauer Sumpio: 203-737-6066
[email protected]
Eileen Moran: 203-737-6066
[email protected]
Suephy C. Chen: 404-712-9660
[email protected]
William S. Weintraub: 404-712-9652
[email protected]
Felicia Warren: 404-727-3683
[email protected]