Trial Outcomes & Findings for Use of Santyl in Diabetic Foot Ulcers (NCT NCT02581488)

NCT ID: NCT02581488

Last Updated: 2018-08-01

Results Overview

Ulcer area was measured using the ARANZ Silhouette digital imaging and measurement device.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

102 participants

Primary outcome timeframe

6 weeks

Results posted on

2018-08-01

Participant Flow

Participant milestones

Participant milestones
Measure	Santyl Collagenase ointment applied topically once per day for up to 6 weeks.	Product Containing Silver Products containing silver was applied per Investigator instructions and instructions for use/package insert for up to 6 weeks. Silver product was not specified by the protocol; Investigators chose the appropriate silver containing product for each diabetic foot ulcer.
Overall Study STARTED	51	51
Overall Study COMPLETED	42	40
Overall Study NOT COMPLETED	9	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Santyl Collagenase ointment applied topically once per day for up to 6 weeks.	Product Containing Silver Products containing silver was applied per Investigator instructions and instructions for use/package insert for up to 6 weeks. Silver product was not specified by the protocol; Investigators chose the appropriate silver containing product for each diabetic foot ulcer.
Overall Study Adverse Event	6	7
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	1	0
Overall Study Non-Compliance	1	0
Overall Study Protocol Violation	0	4

Baseline Characteristics

Use of Santyl in Diabetic Foot Ulcers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Santyl n=51 Participants Collagenase ointment applied topically once per day for up to 6 weeks.	Product Containing Silver n=51 Participants Products containing silver was applied per Investigator instructions and instructions for use/package insert for up to 6 weeks. Silver product was not specified by the protocol; Investigators chose the appropriate silver containing product for each diabetic foot ulcer.	Total n=102 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	37 Participants n=99 Participants	39 Participants n=107 Participants	76 Participants n=206 Participants
Age, Categorical >=65 years	14 Participants n=99 Participants	12 Participants n=107 Participants	26 Participants n=206 Participants
Age, Continuous	56.4 years STANDARD_DEVIATION 13.1 • n=99 Participants	57.6 years STANDARD_DEVIATION 10.8 • n=107 Participants	57 years STANDARD_DEVIATION 12 • n=206 Participants
Sex: Female, Male Female	9 Participants n=99 Participants	15 Participants n=107 Participants	24 Participants n=206 Participants
Sex: Female, Male Male	42 Participants n=99 Participants	36 Participants n=107 Participants	78 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants n=99 Participants	16 Participants n=107 Participants	30 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=99 Participants	35 Participants n=107 Participants	72 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	3 Participants n=99 Participants	3 Participants n=107 Participants	6 Participants n=206 Participants
Race (NIH/OMB) White	47 Participants n=99 Participants	47 Participants n=107 Participants	94 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Region of Enrollment Canada	10 Participants n=99 Participants	10 Participants n=107 Participants	20 Participants n=206 Participants
Region of Enrollment United States	41 Participants n=99 Participants	41 Participants n=107 Participants	82 Participants n=206 Participants
Body Mass Index (BMI)	34.3 kg/m^2 STANDARD_DEVIATION 7.7 • n=99 Participants	33.6 kg/m^2 STANDARD_DEVIATION 6.3 • n=107 Participants	34 kg/m^2 STANDARD_DEVIATION 7.0 • n=206 Participants
Height	69.6 inches STANDARD_DEVIATION 3.2 • n=99 Participants	68.8 inches STANDARD_DEVIATION 3.8 • n=107 Participants	69.2 inches STANDARD_DEVIATION 3.5 • n=206 Participants
Weight	237.6 lbs STANDARD_DEVIATION 56.7 • n=99 Participants	226.6 lbs STANDARD_DEVIATION 49.1 • n=107 Participants	232.1 lbs STANDARD_DEVIATION 53.0 • n=206 Participants
Ankle Brachial Index	1 ABI ratio (mmHg/mmHg) STANDARD_DEVIATION 0.1 • n=99 Participants	1 ABI ratio (mmHg/mmHg) STANDARD_DEVIATION 0.2 • n=107 Participants	1 ABI ratio (mmHg/mmHg) STANDARD_DEVIATION 1 • n=206 Participants
Target Ulcer Area	1.6 cm^2 STANDARD_DEVIATION 1.8 • n=99 Participants	1.7 cm^2 STANDARD_DEVIATION 2.0 • n=107 Participants	1.6 cm^2 STANDARD_DEVIATION 1.9 • n=206 Participants
Foot Perfusion Yes	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Foot Perfusion No	3 Participants n=99 Participants	6 Participants n=107 Participants	9 Participants n=206 Participants
Foot Perfusion N/A, ABI not > 1.2	48 Participants n=99 Participants	45 Participants n=107 Participants	93 Participants n=206 Participants
Target Ulcer Location Forefoot	33 Participants n=99 Participants	42 Participants n=107 Participants	75 Participants n=206 Participants
Target Ulcer Location Hallux	12 Participants n=99 Participants	4 Participants n=107 Participants	16 Participants n=206 Participants
Target Ulcer Location Heel	3 Participants n=99 Participants	4 Participants n=107 Participants	7 Participants n=206 Participants
Target Ulcer Location Medial Forefoot	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Target Ulcer Location Lateral Heel	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Ulcer Duration	106.8 days STANDARD_DEVIATION 75.2 • n=99 Participants	118.1 days STANDARD_DEVIATION 77.7 • n=107 Participants	112.4 days STANDARD_DEVIATION 76.3 • n=206 Participants

PRIMARY outcome

Timeframe: 6 weeks

Ulcer area was measured using the ARANZ Silhouette digital imaging and measurement device.

Outcome measures

Outcome measures
Measure	Santyl n=51 Participants Collagenase ointment applied topically once per day for up to 6 weeks.	Product Containing Silver n=51 Participants Products containing silver was applied per Investigator instructions and instructions for use/package insert for up to 6 weeks. Silver product was not specified by the protocol; Investigators chose the appropriate silver containing product for each diabetic foot ulcer.
Mean Percent Change in Ulcer Area From Baseline to the End of the Treatment.	57.6 percentage of change from baseline (cm2) Standard Deviation 53.1	41.3 percentage of change from baseline (cm2) Standard Deviation 58.3

SECONDARY outcome

Timeframe: 6 weeks

Outcome measures

Outcome measures
Measure	Santyl n=51 Participants Collagenase ointment applied topically once per day for up to 6 weeks.	Product Containing Silver n=51 Participants Products containing silver was applied per Investigator instructions and instructions for use/package insert for up to 6 weeks. Silver product was not specified by the protocol; Investigators chose the appropriate silver containing product for each diabetic foot ulcer.
Target Ulcer Infection Rates in Each Treatment Group During the Treatment Period as Determined by Investigator-reported Adverse Events	5 Participants	11 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 weeks

Days to closure for ulcers that closed by end of treatment period.

Outcome measures

Outcome measures
Measure	Santyl n=51 Participants Collagenase ointment applied topically once per day for up to 6 weeks.	Product Containing Silver n=51 Participants Products containing silver was applied per Investigator instructions and instructions for use/package insert for up to 6 weeks. Silver product was not specified by the protocol; Investigators chose the appropriate silver containing product for each diabetic foot ulcer.
Time to Closure for Ulcers Achieving Closure in Treatment Period	31.1 days Standard Deviation 9	37.1 days Standard Deviation 7.7

OTHER_PRE_SPECIFIED outcome

Timeframe: 10 weeks

Days to closure for ulcers that closed by end of follow-up period.

Outcome measures

Outcome measures
Measure	Santyl n=51 Participants Collagenase ointment applied topically once per day for up to 6 weeks.	Product Containing Silver n=51 Participants Products containing silver was applied per Investigator instructions and instructions for use/package insert for up to 6 weeks. Silver product was not specified by the protocol; Investigators chose the appropriate silver containing product for each diabetic foot ulcer.
Time to Closure for Ulcers Achieving Closure by End of Follow-up	43.0 days Standard Deviation 18.6	50.8 days Standard Deviation 14.6

POST_HOC outcome

Timeframe: 6 weeks

Number of debridements performed during the treatment period by treatment group.

Outcome measures

Outcome measures
Measure	Santyl n=51 Participants Collagenase ointment applied topically once per day for up to 6 weeks.	Product Containing Silver n=51 Participants Products containing silver was applied per Investigator instructions and instructions for use/package insert for up to 6 weeks. Silver product was not specified by the protocol; Investigators chose the appropriate silver containing product for each diabetic foot ulcer.
Incidence of Debridements During Treatment Period	305 occurences	272 occurences

Adverse Events

Santyl

Serious events: 5 serious events

Other events: 25 other events

Deaths: 1 deaths

Product Containing Silver

Serious events: 8 serious events

Other events: 25 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Santyl n=51 participants at risk Collagenase ointment applied topically once per day for up to 6 weeks.	Product Containing Silver n=51 participants at risk Products containing silver was applied per Investigator instructions and instructions for use/package insert for up to 6 weeks. Silver product was not specified by the protocol; Investigators chose the appropriate silver containing product for each diabetic foot ulcer.
Infections and infestations Cellulitis	2.0% 1/51 • Number of events 1 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).	0.00% 0/51 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).
Injury, poisoning and procedural complications Contusion	0.00% 0/51 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).	2.0% 1/51 • Number of events 1 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).
Cardiac disorders Coronary artery disease	2.0% 1/51 • Number of events 1 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).	0.00% 0/51 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).
Injury, poisoning and procedural complications Haemorrhage intracranial	0.00% 0/51 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).	2.0% 1/51 • Number of events 1 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).
Metabolism and nutrition disorders Hyperglycaemia	2.0% 1/51 • Number of events 1 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).	0.00% 0/51 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).
Infections and infestations Infected skin ulcer	0.00% 0/51 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).	2.0% 1/51 • Number of events 1 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).
Musculoskeletal and connective tissue disorders Osteomyelitis	2.0% 1/51 • Number of events 1 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).	5.9% 3/51 • Number of events 3 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).
Renal and urinary disorders Pyelonephritis acute	0.00% 0/51 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).	2.0% 1/51 • Number of events 1 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).
Skin and subcutaneous tissue disorders Subcutaneous emphysema	2.0% 1/51 • Number of events 1 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).	0.00% 0/51 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).
Infections and infestations Wound infection	0.00% 0/51 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).	2.0% 1/51 • Number of events 1 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).
Infections and infestations Wound sepsis	0.00% 0/51 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).	2.0% 1/51 • Number of events 1 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).

Other adverse events

Other adverse events
Measure	Santyl n=51 participants at risk Collagenase ointment applied topically once per day for up to 6 weeks.	Product Containing Silver n=51 participants at risk Products containing silver was applied per Investigator instructions and instructions for use/package insert for up to 6 weeks. Silver product was not specified by the protocol; Investigators chose the appropriate silver containing product for each diabetic foot ulcer.
Skin and subcutaneous tissue disorders Blister	9.8% 5/51 • Number of events 5 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).	0.00% 0/51 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).
Infections and infestations Cellulitis	7.8% 4/51 • Number of events 4 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).	17.6% 9/51 • Number of events 9 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).
Infections and infestations Diabetic foot	7.8% 4/51 • Number of events 6 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).	13.7% 7/51 • Number of events 9 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).
Injury, poisoning and procedural complications Skin abrasion	7.8% 4/51 • Number of events 4 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).	3.9% 2/51 • Number of events 2 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).
Injury, poisoning and procedural complications Wound complication	5.9% 3/51 • Number of events 3 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).	5.9% 3/51 • Number of events 3 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).
Infections and infestations Wound infection	9.8% 5/51 • Number of events 5 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).	7.8% 4/51 • Number of events 4 • 14.5 months Adverse events were coded using Medical Dictionary for Regulatory Activities (MedDRA) adverse event dictionary. The frequency of treatment-emergent adverse events (TEAE) was calculated for each body system, by preferred term, by treatment group, for number of subjects, and the proportion reporting the event for the safety population (SAF).

Additional Information

SR. Clinical Study Manager, US Global Clinical Operations

Smith and Nephew

Phone: +1 817-302-3959

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI to submit results for proposed publication/presentation to the sponsor no later than 90 days prior to the submission. Sponsor to reply within 60 days. Submission of publication/presentation may be delayed an additional 6 months to permit filing of appropriate patent applications. If a multicenter publication is not submitted within 24 months of the conclusion of the study, the Investigator may publish individual site results after review by sponsor.
Publication restrictions are in place

Restriction type: OTHER