Pivotal Trial of Dermagraft(R) to Treat Venous Leg Ulcers | NCT00909870

Label	Type	Description	Intervention Names
1	Experimental	Weekly applications of Dermagraft and compression dressings, in combination with systematic surgical wound debridement.	Device: Dermagraft(R)
2	Active Comparator	Weekly application of compression dressings only, in combination with systematic surgical wound debridement.	Device: Profore

Name	Type	Description	Arm Group Labels	Other Names
Dermagraft(R)	Device	Weekly application of Dermagraft(R) with Profore compression as a secondary layer, in combination with systematic surgical wound debridement.	1

Measure	Description	Time Frame
Complete Healing of the Study Ulcer by Week 16.		16 weeks

Measure	Description	Time Frame
Time-to-Complete Healing	Kaplan-Meier survival analysis of the time to achieve median (50%) Complete Healing response in each treatment group.	From Week 0 visit to date subject's completely healed ulcer is 1st recorded as healed. If subject's ulcer not healed at 16 weeks, the "time until CH" was censored at 112 days.

Measure	Description	Time Frame
Complete Healing by Week 16: Ulcers <= 12 Months Duration		16 weeks

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

>18 years of age
ABI > 0.80
Three or fewer venous leg ulcers, if multiple must be separated by 2 cm
Ultrasound demonstrates venous reflux >0.5 seconds
Study wound present for 1-24 months
Study wound 2-15 sq cm surface area
Clean, granulating wound
Patient able and willing to sign informed consent and comply with study procedures.
Women of childbearing potential must use birth control pills, barriers or abstinence and have a negative pregnancy test.

Exclusion Criteria:

Wound etiology uncertain or not from venous hypertension.
BMI>40
Acute or chronic infectious skin disease
Allergy or intolerance to Profore(R)
Wound infection, cellulitis, osteomyelitis
>2 weeks' treatment with immunosuppressive agents in recent past
Investigational drug use within 30 days
Severe malnutrition, drug and/or alcohol abuse
Malignant disease unless in remission for 5 years
History of radiation at the study site
Other conditions that could impede wound healing
Known history of HIV or AIDS
Prior participation in any Dermagraft study
Treatment with other bioengineered tissue products within 30 days
Unable to understand the aims and objectives of the trial
Inability to comply with study protocol
NYHA Class III or IV CHF
Uncontrolled diabetes mellitus
Dorsal foot ulcer

Name	Affiliation	Role
William Marston, MD	University of North Carolina School of Medicine, Chapel Hill, NC	Principal Investigator
Keith Harding, MD	Cardiff University School of Medicine, Wales, UK	Principal Investigator
David Bergqvist, MD	University of Uppsala, Sweden	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Coastal Clinical Research, Inc.		Mobile	Alabama	36608	United States
Carl T. Hayden VA Medical Center

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Investigational Treatment (Dermagraft Plus Standard-of-Care)	Weekly applications of Dermagraft and compression dressings, in combination with systematic surgical wound debridement.
FG001	Active Control (Standard-of-Care)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Complete Healing of the Study Ulcer by Week 16.

Intent-to-Treat population

Posted

Number

participants

16 weeks

ID	Title	Description
OG000	Investigational Treatment (Dermagraft Plus Standard-of-Care)	Weekly applications of Dermagraft and compression dressings, in combination with systematic surgical wound debridement.
OG001	Control (Standard-of-Care)	Weekly application of compression dressings only, in combination with systematic surgical wound debridement.

Units	Counts
Participants	OG000274 OG001263

Title

Denominators

Categories

Title	Measurements
	OG000201 OG001176

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	H0: the proportion of responders in the Dermagraft group = the proportion of responders in the Control group. HA: the proportion of responders in the Dermagraft group ≠ the proportion of responders in the Control group. The proportion of responders in the Dermagraft group was compared with the proportion of responders in the control group using the uncorrected chi-square test for 2x2 contingency tables. The difference between the groups was expected to be 13%.	Chi-squared	Unadjusted	0.1030	This p-value did not meet the prespecified threshold for statistical significance of < 0.05	Difference in proportions	6.5			2-Sided	95

Secondary

Time-to-Complete Healing

Kaplan-Meier survival analysis of the time to achieve median (50%) Complete Healing response in each treatment group.

Intent-to-Treat population

Posted

Median

Inter-Quartile Range

days

From Week 0 visit to date subject's completely healed ulcer is 1st recorded as healed. If subject's ulcer not healed at 16 weeks, the "time until CH" was censored at 112 days.

ID	Title	Description
OG000	Investigational Treatment (Dermagraft Plus Standard-of=- Care)	Weekly applications of Dermagraft and compression dressings, in combination with systematic surgical wound debridement.
OG001	Control (Standard-of-Care)	Weekly application of compression dressings only, in combination with systematic surgical wound debridement.

Units	Counts
Participants	OG000

Other Pre-specified

Complete Healing by Week 16: Ulcers <= 12 Months Duration

Pre-specified Subgroup of the Intent-to-Treat Population

Posted

Number

participants

16 weeks

ID	Title	Description
OG000	Investigational Treatment (Dermagraft Plus Standard-of-Care)	Weekly applications of Dermagraft and compression dressings, in combination with systematic surgical wound debridement.
OG001	Control (Standard-of-Care)	Weekly application of compression dressings only, in combination with systematic surgical wound debridement.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Statistical Information
Anemia	Blood and lymphatic system disorders	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Acute Myocardial Infarction	Cardiac disorders	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Angina Unstable	Cardiac disorders	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Atrial Fibrilation	Cardiac disorders	EG0000 events0 affected274 at risk EG0013 events3 affected263 at risk
Cardiac Failure	Cardiac disorders	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Cardiac failure congestive	Cardiac disorders	EG0000 events0 affected274 at risk EG0012 events2 affected263 at risk
Cardio-respiratory arrest	Cardiac disorders	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Coronary artery disease	Cardiac disorders	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Myocardial infarction	Cardiac disorders	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Sick Sinus Syndrome	Cardiac disorders	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Constipation	Gastrointestinal disorders	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Diarrhea	Gastrointestinal disorders	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Inguinal hernia	Gastrointestinal disorders	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Asthenia	General disorders	EG0001 events1 affected274 at risk EG0011 events1 affected263 at risk
Death	General disorders	EG0003 events3 affected274 at risk EG0012 events2 affected263 at risk
Drug intolerance	General disorders	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Oedema peripheral	General disorders	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Abscess	Infections and infestations	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Abscess limb	Infections and infestations	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Appendicitis	Infections and infestations	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Bronchitis	Infections and infestations	EG0000 events0 affected274 at risk EG0012 events2 affected263 at risk
Cellulitis	Infections and infestations	EG0002 events2 affected274 at risk EG0011 events1 affected263 at risk
Clostridial infection	Infections and infestations	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Gastroenteritis	Infections and infestations	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Infected skin ulcer	Infections and infestations	EG0002 events2 affected274 at risk EG0012 events2 affected263 at risk
Laryngitis	Infections and infestations	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Lower respiratory tract infection	Infections and infestations	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Pelvic abscess	Infections and infestations	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Peritonitis bacterial	Infections and infestations	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Pneumonia	Infections and infestations	EG0002 events2 affected274 at risk EG0013 events3 affected263 at risk
Sepsis	Infections and infestations	EG0001 events1 affected274 at risk EG0011 events1 affected263 at risk
Upper respiratory tract infection	Infections and infestations	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Urinary tract infection	Infections and infestations	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Facial bones fractures	Injury, poisoning and procedural complications	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Hip fracture	Injury, poisoning and procedural complications	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Pelvic fracture	Injury, poisoning and procedural complications	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Post procedural haematoma	Injury, poisoning and procedural complications	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Angiogram	Investigations	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Cardiac stress test	Investigations	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Hypoglycemia	Metabolism and nutrition disorders	EG0001 events1 affected274 at risk EG0011 events1 affected263 at risk
Back pain	Musculoskeletal and connective tissue disorders	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Joint effusion	Musculoskeletal and connective tissue disorders	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Lung neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Cerebrovascular accident	Nervous system disorders	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Epilepsy	Nervous system disorders	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Subarachnoid haemorrhage	Nervous system disorders	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Haematuria	Renal and urinary disorders	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Renal failure acute	Renal and urinary disorders	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Cough	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Erythema	Skin and subcutaneous tissue disorders	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Pupura	Skin and subcutaneous tissue disorders	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Implantable defibrilator replacement	Surgical and medical procedures	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Inguinal hernia repair	Surgical and medical procedures	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Therapy regimen changed	Surgical and medical procedures	EG0002 events2 affected274 at risk EG0010 events0 affected263 at risk
Varicose vein operation	Surgical and medical procedures	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk
Venous operation	Surgical and medical procedures	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Hypertension	Vascular disorders	EG0001 events1 affected274 at risk EG0010 events0 affected263 at risk
Hypertensive crisis	Vascular disorders	EG0000 events0 affected274 at risk EG0011 events1 affected263 at risk

ID	Term
D014648	Varicose Veins
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D007871	Leg Ulcer
D012883	Skin Ulcer
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Title	Description
BG000	Investigational Treatment (Dermagraft Plus Standard-of-Care)	Weekly applications of Dermagraft and compression dressings, in combination with systematic surgical wound debridement.
BG001	Control (Standard-of-Care)	Weekly application of compression dressings only, in combination with systematic surgical wound debridement.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Investigational Treatment (Dermagraft Plus Standard-of-Care)	Weekly applications of Dermagraft and compression dressings, in combination with systematic surgical wound debridement.			28	274	168	274
EG001	Control (Standard-of-Care)	Weekly application of compression dressings only, in combination with systematic surgical wound debridement.			24	263	157	263

Term	Organ System	Statistical Information
Skin Ulcer	Skin and subcutaneous tissue disorders	EG00077 events77 affected274 at risk EG00160 events60 affected263 at risk
Infected skin ulcer	Infections and infestations	EG00022 events22 affected274 at risk EG00125 events25 affected263 at risk
Excoriation	Injury, poisoning and procedural complications	EG00020 events20 affected274 at risk EG00116 events16 affected263 at risk
Hypertension	Vascular disorders	EG00014 events14 affected274 at risk EG00113 events13 affected263 at risk
Nasopharyngitis	Infections and infestations	EG00018 events18 affected274 at risk EG00118 events18 affected263 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	EG00017 events17 affected274 at risk EG00125 events25 affected263 at risk