Study Design
It was a Multicenter, randomized, open label, parallel-group, comparative, prospective clinical study to evaluate the efficacy and safety of polyherbal oil compared with betadine 10% ointment in subjects with diabetic non-healing wound. (CTRI No.:- CTRI/2019/09/021095).
All procedures followed the tenets of the Declaration of Helsinki, were in accordance with all regulatory standards, were approved by an Institutional Review Board and all subjects signed an informed consent form. Protocols, Informed consent and study related documents were approved by an Institutional Ethical Committee of the respective study sites.
Subjects
The study was consisted of 83 screened subjects of diabetic non-healing wound. In that 08 were screen failure, 01 subject had withdrawn the consent before randomization hence, 74 subjects of diabetic non-healing wound were randomized in the ratio of 1:1 in polyherbal oil and betadine 10% ointment respectively. 01 subject had withdrawn the consent after randomization, 06 Lost to follow-up hence, 67 subjects completed the study.
All the subjects were advised for the topical application of Polyherbal oil ≤ 5ml per application or Betadine 10% ointment depending on wound size once on alternate day with dressing as per randomization. The treatment continued for 45 days with periodic follow-up on 9th, 18th, 27th, 36th and 45th day from start of treatment.
Study Eligibility Criteria
Subjects meeting all of the following criteria were recruited for the trial:
- Subjects, male or female, aged 25 to 75 years (inclusive) with Type 1 or Type 2 diabetes undergoing therapy for Glycaemic control.
- Subject has glycosylated Haemoglobin, HbA1C, ≤ 10%
- Subject with diagnosis of diabetic non-healing wound.
- Wound size (area) is ≤ 25 cm2 (Post-debridement) at the screening visit.
- There is a minimum 3 cm margin between the qualifying target wound and any other wound on the specified body part, post debridement.
- Unresponsive to wound care and open for at least 10 days at the time of the Screening Visit.
- Wound is non-infected as determined by clinical assessment and complete hemogram (CBC).
- Subject, if female of child-bearing potential, has a negative urine pregnancy test at Screening and willing to use acceptable methods of contraception (birth control pills, barriers) or abstinence throughout the Study.
- Subject is able and willing to comply with Study Procedures and adhere to protocol during the Study in the opinion of Investigator.
- A Subject or LAR agrees to sign informed consent form.
Treatment and compliance
The subjects (n = 74) were randomly assigned to either of the arms in 1:1 proportion. Randomization was carried out using randomization list. Prior to the randomization, site specific randomization list was generated by the statistician.. Each subject of diabetic non-healing wound were advised for the topical application of Polyherbal oil ≤ 5ml per application or Betadine 10% ointment depending on wound size once on alternate day with dressing as per randomization. The treatment continued for 45 days with periodic follow-up on 9th, 18th, 27th, 36th and 45th day from start of treatment.
Time and events schedule
Total 7 visits had conducted during this entire study after baseline investigation (visit 1). Visit 2 (day 1), Visit 3 (day 9±2), Visit 4 (day 18±2), Visit 5 (day 27±2), Visit 6 (day 36±2) and visit 7 (Day 45±4), and site visit for IP application and dressing on day 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, and day 45. Test product or comparator dispensed and applied during this visit as per randomization schedule.
Assessment at screening visit was done and written informed consent was taken from the subject. Evaluation of Inclusion and Exclusion criteria (Subject must meet all the Inclusion criteria and none of the exclusion criteria): Demographics, complete medical history, past history and history of any other treatment, Surgical or sharp debridement of target wound if required along with documentation of type of debridement (e.g. callus removal, sharp or surgical), reason for debridement were done at screening visit.
Laboratory Tests (Haematology tests, random blood sugar and HbA1c) Urine pregnancy test for child bearing potential female subject were done at screening and end of the study visits.
Vital signs including pulse, BP, temperature, body weight, and physical examination, target wound size assessment and measurement by Vernier caliper or ruler, pain scale assessment, edema scale assessment, Granulation tissue assessment, Exudate type and amount assessment, Proliferation assessment, Lesion (target wound) photograph, Recording of concomitant medication, Dietary and lifestyle counselling were done at all follow-up visits.
Study Period
The study treatment period was of 45 days. The first subject was screened on 30-Sep-2019 and the subject was screed failed. The last subject was screened on 17-Dec-2020 and randomized on 10-Dec-2020. The study of first subject was not completed due to screen failed and the study of last subject was completed on 25-Jan-2021.
Safety and efficacy parameters
Evaluation of wound and vital signs including pulse, BP, temperature, body weight, and physical examination, target wound size assessment and measurement by Vernier caliper or ruler, pain scale assessment, edema scale assessment, Granulation tissue assessment, Exudate type and amount assessment, Proliferation assessment, Lesion (target wound) photograph, Recording of concomitant medication, Dietary and lifestyle counselling were done to evaluate the safety of polyherbal oil. All SAE and AE regardless of treatment group or suspected causal relationship to study drug were recorded on the adverse event page(s) of the Case Record Form.
The patient who was having COVID-19 related symptoms was not included in the study. During study no patient was observed to have COVID-19 related symptoms. We informed site regarding precautions to be taken for COVID-19 and site ensured that they took all the measures while evaluation of all the patients. No patient was observed with any sign or symptom of COVID-19 during the whole study.
Site team were in continuous contact with subjects over telephone for any side effects or new symptoms or worsening of any symptoms.
Primary Efficacy Parameter
The evaluations of Percentage change in wound size and granulation from baseline to end of study treatment were done as well defined scale given in Annexure 1 and Annexure 2 respectively.
Secondary Efficacy Parameter
The evaluations on effect of polyherbal oil in reduction of exude type, exudate amount, pain, edema and proliferation of epithelialization were assessed as per given scale in Annexure 3,4,5,6 and 7 respectively.