Trial Outcomes & Findings for Insulin Complexation With Hydroxypropyl-beta-cyclodextrin: Use of the Complex in Gel for Healing of Pressure Ulcers (NCT NCT02418676)

Results Overview

Every three days the pressure ulcers (PUs) of all patients were measured and photographed again, resulting in a total of six measurements per patient. The photos were evaluated for measurement of PUs and any kind of irritation. At the end of this stage, the properly gathered study data was interpreted using the analysis software Mobile Wound Analyzer® (MOWA). Healing efficacy indices (% EI) were calculated as percentage reduction in the wound size at days 3, 6, 9, 12 and 15 from treatment beginning (d0). The % EI of the wound size was calculated by the following equation: %EI= ((Vsp.day-Vi)/Vi))x100. Vsp.day refers to the diameter (mm) values measured at day 3, 6, 9,12 and 15, while Vi refers to the baseline value measured before treatment (d0). The most representative result of treatment efficacy was observed on day 15, therefore it was used to calculate the % EI. For each group assessed, it was calculated the mean % EI of the five patients, resulting in a single value.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

15 participants

Primary outcome timeframe

Measured every 3 days for 15 days

Results posted on

2016-01-14

Participant Flow

A randomized, double-blind, prospective clinical trial was conducted from March 2013 to April 2014 at the Hospital Universitário Regional de Maringá (HUM), Paraná, Brazil, in order to determine the safety and efficacy of gel in patients hospitalized in the Intensive Care Unit.

The volunteers were Brazilian, bedridden, both genders, between 45 and 75 years old and diabetic or not. Hyperglycemic volunteers and those with pressure ulcers other than grade II were excluded from the study. Grade II pressure ulcers were selected as they are a superficial lesion, with little tissue loss, and allow easy visualization of healing.

Participant milestones

Participant milestones
Measure	Gel With HPβCD-I Complex A quantity of 5 grams of gel with hydroxypropyl-beta-cyclodextrin complexed with insulin (HPβCD-I) was placed on the pressure ulcer, previously cleaned with saline, and covered with sterile gauze and a transparent film. Gel with HPβCD-I complex: Initially, the pressure ulcer was cleaned with saline. With the aid of a paper ruler, the ulcer was measured and photographed, as the ruler included the date and the initials of the patient. After measuring, a quantity of 5 grams of gel with HPβCD-I complex was placed on the pressure ulcer and covered with sterile gauze and a transparent film. The curative was changed once a day during the treatment period, unless there was leakage of fluid, contamination, or signs of infection. Every three days the pressure ulcers of all patients were measured and photographed again, resulting in a total of six measurements per patient. The photos of pressure ulcers were evaluated for measurement of pressure ulcers and any kind of irritation.	Gel With Insulin A quantity of 5 grams of gel with insulin was placed on the pressure ulcer, previously cleaned with saline, and covered with sterile gauze and a transparent film. Gel with insulin: Initially, the pressure ulcer was cleaned with saline. With the aid of a paper ruler, the ulcer was measured and photographed, as the ruler included the date and the initials of the patient. After measuring, a quantity of 5 grams of gel with insulin was placed on the pressure ulcer and covered with sterile gauze and a transparent film. The curative was changed once a day during the treatment period, unless there was leakage of fluid, contamination, or signs of infection. Every three days the pressure ulcers of all patients were measured and photographed again, resulting in a total of six measurements per patient. The photos of pressure ulcers were evaluated for measurement of pressure ulcers and any kind of irritation.	Control Gel A quantity of 5 grams of gel without active was placed on the pressure ulcer, previously cleaned with saline, and covered with sterile gauze and a transparent film. Control gel: Initially, the pressure ulcer was cleaned with saline. With the aid of a paper ruler, the ulcer was measured and photographed, as the ruler included the date and the initials of the patient. After measuring, a quantity of 5 grams of control gel was placed on the pressure ulcer and covered with sterile gauze and a transparent film. The curative was changed once a day during the treatment period, unless there was leakage of fluid, contamination, or signs of infection. Every three days the pressure ulcers of all patients were measured and photographed again, resulting in a total of six measurements per patient. The photos of pressure ulcers were evaluated for measurement of pressure ulcers and any kind of irritation.
Overall Study STARTED	5	5	5
Overall Study COMPLETED	5	5	5
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Insulin Complexation With Hydroxypropyl-beta-cyclodextrin: Use of the Complex in Gel for Healing of Pressure Ulcers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gel With HPβCD-I Complex n=5 Participants A quantity of 5 grams of gel with hydroxypropyl-beta-cyclodextrin complexed with insulin (HPβCD-I) was placed on the pressure ulcer, previously cleaned with saline, and covered with sterile gauze and a transparent film. Gel with HPβCD-I complex: Initially, the pressure ulcer was cleaned with saline. With the aid of a paper ruler, the ulcer was measured and photographed, as the ruler included the date and the initials of the patient. After measuring, a quantity of 5 grams of gel with HPβCD-I complex was placed on the pressure ulcer and covered with sterile gauze and a transparent film. The curative was changed once a day during the treatment period, unless there was leakage of fluid, contamination, or signs of infection. Every three days the pressure ulcers of all patients were measured and photographed again, resulting in a total of six measurements per patient. The photos of pressure ulcers were evaluated for measurement of pressure ulcers and any kind of irritation.	Gel With Insulin n=5 Participants A quantity of 5 grams of gel with insulin was placed on the pressure ulcer, previously cleaned with saline, and covered with sterile gauze and a transparent film. Gel with insulin: Initially, the pressure ulcer was cleaned with saline. With the aid of a paper ruler, the ulcer was measured and photographed, as the ruler included the date and the initials of the patient. After measuring, a quantity of 5 grams of gel with insulin was placed on the pressure ulcer and covered with sterile gauze and a transparent film. The curative was changed once a day during the treatment period, unless there was leakage of fluid, contamination, or signs of infection. Every three days the pressure ulcers of all patients were measured and photographed again, resulting in a total of six measurements per patient. The photos of pressure ulcers were evaluated for measurement of pressure ulcers and any kind of irritation.	Control Gel n=5 Participants A quantity of 5 grams of gel without active was placed on the pressure ulcer, previously cleaned with saline, and covered with sterile gauze and a transparent film. Control gel: Initially, the pressure ulcer was cleaned with saline. With the aid of a paper ruler, the ulcer was measured and photographed, as the ruler included the date and the initials of the patient. After measuring, a quantity of 5 grams of control gel was placed on the pressure ulcer and covered with sterile gauze and a transparent film. The curative was changed once a day during the treatment period, unless there was leakage of fluid, contamination, or signs of infection. Every three days the pressure ulcers of all patients were measured and photographed again, resulting in a total of six measurements per patient. The photos of pressure ulcers were evaluated for measurement of pressure ulcers and any kind of irritation.	Total n=15 Participants Total of all reporting groups
Age, Customized >45 and <75 years	5 participants n=93 Participants	5 participants n=4 Participants	5 participants n=27 Participants	15 participants n=483 Participants
Sex: Female, Male Female	3 Participants n=93 Participants	2 Participants n=4 Participants	4 Participants n=27 Participants	9 Participants n=483 Participants
Sex: Female, Male Male	2 Participants n=93 Participants	3 Participants n=4 Participants	1 Participants n=27 Participants	6 Participants n=483 Participants

PRIMARY outcome

Timeframe: Measured every 3 days for 15 days

Population: Brazilian, bedridden, of both genders, aged between 45 and 75 years old and diabetic or not. Hyperglycemic volunteers and those with pressure ulcers other than grade II were excluded from the study. Grade II pressure ulcers were selected as they are a superficial lesion, with little tissue loss, and allow easy visualization of healing.

Every three days the pressure ulcers (PUs) of all patients were measured and photographed again, resulting in a total of six measurements per patient. The photos were evaluated for measurement of PUs and any kind of irritation. At the end of this stage, the properly gathered study data was interpreted using the analysis software Mobile Wound Analyzer® (MOWA). Healing efficacy indices (% EI) were calculated as percentage reduction in the wound size at days 3, 6, 9, 12 and 15 from treatment beginning (d0). The % EI of the wound size was calculated by the following equation: %EI= ((Vsp.day-Vi)/Vi))x100. Vsp.day refers to the diameter (mm) values measured at day 3, 6, 9,12 and 15, while Vi refers to the baseline value measured before treatment (d0). The most representative result of treatment efficacy was observed on day 15, therefore it was used to calculate the % EI. For each group assessed, it was calculated the mean % EI of the five patients, resulting in a single value.

Outcome measures

Outcome measures
Measure	Gel With HPβCD-I Complex n=5 Participants A quantity of 5 grams of gel with hydroxypropyl-beta-cyclodextrin complexed with insulin (HPβCD-I) was placed on the pressure ulcer, previously cleaned with saline, and covered with sterile gauze and a transparent film. Gel with HPβCD-I complex: Initially, the pressure ulcer was cleaned with saline. With the aid of a paper ruler, the ulcer was measured and photographed, as the ruler included the date and the initials of the patient. After measuring, a quantity of 5 grams of gel with HPβCD-I complex was placed on the pressure ulcer and covered with sterile gauze and a transparent film. The curative was changed once a day during the treatment period, unless there was leakage of fluid, contamination, or signs of infection. Every three days the pressure ulcers of all patients were measured and photographed again, resulting in a total of six measurements per patient. The photos of pressure ulcers were evaluated for measurement of pressure ulcers and any kind of irritation.	Gel With Insulin n=5 Participants A quantity of 5 grams of gel with insulin was placed on the pressure ulcer, previously cleaned with saline, and covered with sterile gauze and a transparent film. Gel with insulin: Initially, the pressure ulcer was cleaned with saline. With the aid of a paper ruler, the ulcer was measured and photographed, as the ruler included the date and the initials of the patient. After measuring, a quantity of 5 grams of gel with insulin was placed on the pressure ulcer and covered with sterile gauze and a transparent film. The curative was changed once a day during the treatment period, unless there was leakage of fluid, contamination, or signs of infection. Every three days the pressure ulcers of all patients were measured and photographed again, resulting in a total of six measurements per patient. The photos of pressure ulcers were evaluated for measurement of pressure ulcers and any kind of irritation.	Control Gel n=5 Participants A quantity of 5 grams of gel without active was placed on the pressure ulcer, previously cleaned with saline, and covered with sterile gauze and a transparent film. Control gel: Initially, the pressure ulcer was cleaned with saline. With the aid of a paper ruler, the ulcer was measured and photographed, as the ruler included the date and the initials of the patient. After measuring, a quantity of 5 grams of control gel was placed on the pressure ulcer and covered with sterile gauze and a transparent film. The curative was changed once a day during the treatment period, unless there was leakage of fluid, contamination, or signs of infection. Every three days the pressure ulcers of all patients were measured and photographed again, resulting in a total of six measurements per patient. The photos of pressure ulcers were evaluated for measurement of pressure ulcers and any kind of irritation.
Efficacy Index (%EI)	82.76 percentage (%) Interval 78.25 to 86.15	43.66 percentage (%) Interval 39.73 to 47.03	14.58 percentage (%) Interval 12.53 to 16.25

SECONDARY outcome

Timeframe: Assessed daily at 04 h, 10 h, 16 h and 22 h for 15 days

Population: Brazilian, bedridden, of both genders, aged between 45 and 75 years old and diabetic or not. Hyperglycemic volunteers and those with pressure ulcers other than grade II were excluded from the study.

Dosages were provided four times daily (04h, 10h, 16h and 22h) to each patient during the 15-day study period, giving a total of 60 doses. To obtain these dosages, a drop of blood of patients was placed on a colorimetric strip and blood glucose was measured with the use of an Accu Check Active® glucose meter. The mean of 60 dosages was calculated for each patient at the end of 15 days. For each group assessed, it was calculated the mean of the measurements of the five patients, resulting in a single value.

Outcome measures

Outcome measures
Measure	Gel With HPβCD-I Complex n=5 Participants A quantity of 5 grams of gel with hydroxypropyl-beta-cyclodextrin complexed with insulin (HPβCD-I) was placed on the pressure ulcer, previously cleaned with saline, and covered with sterile gauze and a transparent film. Gel with HPβCD-I complex: Initially, the pressure ulcer was cleaned with saline. With the aid of a paper ruler, the ulcer was measured and photographed, as the ruler included the date and the initials of the patient. After measuring, a quantity of 5 grams of gel with HPβCD-I complex was placed on the pressure ulcer and covered with sterile gauze and a transparent film. The curative was changed once a day during the treatment period, unless there was leakage of fluid, contamination, or signs of infection. Every three days the pressure ulcers of all patients were measured and photographed again, resulting in a total of six measurements per patient. The photos of pressure ulcers were evaluated for measurement of pressure ulcers and any kind of irritation.	Gel With Insulin n=5 Participants A quantity of 5 grams of gel with insulin was placed on the pressure ulcer, previously cleaned with saline, and covered with sterile gauze and a transparent film. Gel with insulin: Initially, the pressure ulcer was cleaned with saline. With the aid of a paper ruler, the ulcer was measured and photographed, as the ruler included the date and the initials of the patient. After measuring, a quantity of 5 grams of gel with insulin was placed on the pressure ulcer and covered with sterile gauze and a transparent film. The curative was changed once a day during the treatment period, unless there was leakage of fluid, contamination, or signs of infection. Every three days the pressure ulcers of all patients were measured and photographed again, resulting in a total of six measurements per patient. The photos of pressure ulcers were evaluated for measurement of pressure ulcers and any kind of irritation.	Control Gel n=5 Participants A quantity of 5 grams of gel without active was placed on the pressure ulcer, previously cleaned with saline, and covered with sterile gauze and a transparent film. Control gel: Initially, the pressure ulcer was cleaned with saline. With the aid of a paper ruler, the ulcer was measured and photographed, as the ruler included the date and the initials of the patient. After measuring, a quantity of 5 grams of control gel was placed on the pressure ulcer and covered with sterile gauze and a transparent film. The curative was changed once a day during the treatment period, unless there was leakage of fluid, contamination, or signs of infection. Every three days the pressure ulcers of all patients were measured and photographed again, resulting in a total of six measurements per patient. The photos of pressure ulcers were evaluated for measurement of pressure ulcers and any kind of irritation.
Blood Glucose Tests in Order to Assess Whether the Gel With Hydroxypropyl-beta-cyclodextrin Complexed With Insulin (HPβCD-I) or With Insulin Could Cause an Increase in the Rate of Insulin in the Blood of Patients	167.20 mg/dL Interval 153.92 to 208.9	168.88 mg/dL Interval 155.12 to 209.39	196.07 mg/dL Interval 103.0 to 325.0

Adverse Events

Gel With HPβCD-I Complex

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Gel With Insulin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Control Gel

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dra. Graciette Matioli

State University of Maringá - Paraná - Brazil

Phone: 55 44 3011-3868

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place