|Year : 2022 | Volume
| Issue : 3 | Page : 142-147
Efficacy of the topical application of C1 herbal oil on superficial external wounds and split thickness skin graft donor sites for wound healing: A study protocol for prospective, randomized, controlled, two-phased clinical trial
Maneesh Singhal1, Shashank Chauhan1, Shruti Khanduri2, Hemanta Kumar Panigrahi2, Lalita Sharma2, Bhogavalli Chandrasekhar Rao2, Neera Vyas2, Madan Mohan Padhi2, Kartar Singh Dhiman2, Narayanam Srikanth2
1 Department of Plastic surgery Burns and Plastic Surgery, All India Institute of Medical Sciences (AIIMS), Janakpuri, New Delhi, India
2 Central Council for Research in Ayurvedic Sciences (CCRAS), Janakpuri, New Delhi, India
|Date of Submission||16-Jun-2022|
|Date of Acceptance||21-Sep-2022|
|Date of Web Publication||01-Nov-2022|
Dr. Shruti Khanduri
Central Council for Research in Ayurvedic Sciences (CCRAS), Janakpuri, New Delhi
Source of Support: None, Conflict of Interest: None
BACKGROUND: C1 herbal oil is developed by Central Council for Research in Ayurvedic Sciences, Ministry of Ayush, Government of India and is based on Local Health traditions (LHTs) for wound healing. This study is planned to assess the efficacy of C1 herbal oil on Superficial External Wounds and Split Thickness Skin Graft (STSG) donor sites for wound healing. MATERIALS AND METHODS: The study is a prospective, open-label, randomized, controlled, two-phased clinical trial for a duration of 28 days. Outpatients of age group 18–60 years, of either sex requiring STSG coverage of at least two strips will be recruited in Phase 1 of the study. The donor site will receive the topical application of C1 herbal oil prior to the standard dressing, whereas the normal saline will be applied on the control site. The dressings will not be changed, except when it is fully soaked with exudates or will easily fall off or show any signs of infection. Subjects with superficial external wounds will be recruited in Phase 2 of the study. The test site will receive C1 herbal oil-impregnated dressings, whereas the other group will receive saline gauze dressing, to be changed every 24 h or earlier in case of soakage or accidental removal. The duration of wound healing was the primary outcome measure. The pain during dressing change will be evaluated with a visual analog scale and wound assessment by Bates Jensen Wound Assessment Tool. DISCUSSION: Ayurveda herbal wound dressing may significantly reduce the time for epithelialization of wounds. It may be beneficial in decreasing healthcare costs besides including Ayurveda medicines in mainstream clinical medicine for wound care. TRIAL REGISTRATION: Clinical trials registry- India: CTRI/2017/10/010150
Keywords: C1 herbal oil, donor site, split thickness skin graft, superficial external wound, surgical wound healing, wound dressing
|How to cite this article:|
Singhal M, Chauhan S, Khanduri S, Panigrahi HK, Sharma L, Rao BC, Vyas N, Padhi MM, Dhiman KS, Srikanth N. Efficacy of the topical application of C1 herbal oil on superficial external wounds and split thickness skin graft donor sites for wound healing: A study protocol for prospective, randomized, controlled, two-phased clinical trial. J Res Ayurvedic Sci 2022;6:142-7
|How to cite this URL:|
Singhal M, Chauhan S, Khanduri S, Panigrahi HK, Sharma L, Rao BC, Vyas N, Padhi MM, Dhiman KS, Srikanth N. Efficacy of the topical application of C1 herbal oil on superficial external wounds and split thickness skin graft donor sites for wound healing: A study protocol for prospective, randomized, controlled, two-phased clinical trial. J Res Ayurvedic Sci [serial online] 2022 [cited 2022 Dec 9];6:142-7. Available from: http://www.jrasccras.com/text.asp?2022/6/3/142/360161
| Introduction|| |
Background and rationale
Every tissue disruption of normal anatomic structure with consecutive loss of function can be described as a wound. The Science of wound healing has been in existence since antiquity. Wound healing is a complex physiological multifaceted process involving phases of pathophysiological, biochemical, and cellular changes namely hemostasis, inflammation, proliferation, and tissue remodeling or resolution. Various factors affect wound healing by interfering one or more phases in this process, thus causing improper or impaired tissue repair. Scientific advances unceasingly reveal the complexity of wound-healing process. As per a 2018 retrospective analysis of Medicare beneficiaries, ~8.2 million people had wounds with or without infections. It is estimated that 1 to 2% of the population will experience a chronic wound during their lifetime in developed countries. Non-healing or chronic wounds result in enormous health care expenditures and pose a substantial clinical, social, and economic challenge due to aging population and increasing prevalence of diabetes and obesity worldwide.
Ayurveda has a rich knowledge on wound healing. Various plants/plant extracts/decoctions or pastes are also used by tribal and folklore traditions in India for treatment of cuts, wounds, and burns.
In Ayurveda, the concept of different types of the wound is described under Vrana (wound). The concepts and principles of Vrana such as etiology classification, examination, treatment, bandaging, complications etc. mentioned in Ayurveda classics are relevant enough even in twenty-first century. Ayurveda has broadly described about treatment principles of wound management and classified the medicines related to Vrana Shodhana (wound cleaning) and Vrana Ropana (wound healing). Acharya Sushruta, the father of surgery, has explained sixty types of procedures such as healing, purification, disinfection, bandaging, pigmenting procedures, and fumigation for Vrana Shodhana and Vrana Ropana in order to achieve early healing and better approximation without any complication or acceptable scar. Numerous Ayurveda herbal medicines have been advocated for topical application and systemic use.
The main objective of wound management is either to shorten the time required for healing process or to minimize the undue effects. Ayurveda Herbal medicines are more potent healers because they promote the repair mechanisms in a natural way. Plant-based therapy not only accelerates healing process, moreover, also maintain the aesthetics.
Lacunae in the knowledge and the need for the study
Wound care professionals face several challenges, which continues the search for an ideal dressing material. Conventional medicines have limitations of allergy, resistance, cost, etc., which has inclined the treating physicians to contemplate alternative approaches to wound healing and validating their use as per latest technology. Decrease in new antibiotics and emergence of multi-resistant organisms have led to the probing of ancient healing methods in wound management by using traditional and alternative medicine by the wound care professionals. Due to presence of various valuable active in plants, the phyto-constituents have immense potential for management and treatment of wounds.
Scientific evidence on herbal dressing used in the study
C1 herbal oil is based on Local Health traditions (LHTs) used for wounds and skin diseases. Based on the leads from LHTs, the Council has carried out the drug development process. The quality standards for use of this drug have been developed and it was subjected to dermal toxicity on Wistar rats and biological activity The study concluded that the medicine in question was safe for topical application for a period of 28 days up to a dose of 1000 mg/kg. It also showed anti-inflammatory activity on Carrageenan induced hind paw edema in rats. Additionally, it displayed promising wound healing activity. Therefore, the present clinical trial has been planned to evaluate the efficacy of C1 herbal oil in Split Thickness Skin Graft (STSG) donor sites and superficial external wounds.
The study is designed with an objective to assess the Safety of the C1 oil in terms of adverse drug events, i.e., blistering and contact dermatitis. The study has been planned to compare the healing time of Superficial external wounds and STSG donor sites receiving C1 oil with control wound site receiving saline. The study aspires to further compare the incidence of infections of Superficial external wounds and STSG donor sites receiving C1 oil with control site receiving saline. The trial has also been designed to determine the wound complications from the use of C1 oil, if any.
The study is a prospective, randomized, controlled, open label, two phased clinical trial. The duration of the study intervention will be of 28 days. Participants with raw areas requiring STSG coverage of at least two strips will be recruited in Phase 1 of the study. Based on results of Phase 1, participants with superficial external wounds will be recruited in Phase 2. Trial has been registered at CTRI/2017/10/010150.
| Materials and Methods|| |
The participants will be recruited at All India Institute of Medical Sciences, New Delhi.
Participant selection and enrolment criteria
Participants aged 18–60 years of either sex, with a raw area requiring STSG of at least two strips in phase 1 and superficial external wounds requiring dressing in phase 2 will be enrolled in study. The detail of the participant timeline is depicted in [Figure 1].
Participants having known allergy/hypersensitivity to any of the components of the dressing, Fracture/ DVT of lower extremity, skin disorder that is chronic or currently active, polytrauma participants, wound at the surgical site prior to surgery or requiring full-thickness graft, neurological deficit at the wound site (hemiplegia), hemoglobin level <7.0 g/dL, serum albumin <3 g/dl, hepatic failure, renal failure, coagulopathy, known cases of diabetes mellitus, participants who in the opinion of the investigator, may not complete the study for any reason, immunocompromised participants such as with acquired immunodeficiency syndrome (AIDS) or receiving systemic immunosuppression medications, participants have psychiatric disorders or physical disabilities that hinders study participation, pregnant or lactating women, participant has history of poor wound healing, history of smoking/ drug/alcohol abuse, subjects with poor prognosis and unlikely to survive the trial period, participants will be a reference wound cannot be treated in isolation from other wounds will be excluded from the study enrollment.
Development of SAE necessitating hospitalization, failure to adhere to protocol requirements, participant consent withdrawal, and disease progression are the criteria for withdrawal of the participants from the study prior to expected completion.
Handling of withdrawals
Any participant who withdrew from the trial will be planned to undergo a complete final examination at least undergo a final telephone interview.
This study has been designed to assess the efficacy of topical application of an herbal formulation coded as C1 herbal oil having wound healing properties on Superficial External Wounds and STSG donor sites for surgical wound healing in the intervention group. The Control group will receive saline application followed by standard dressing.
The participants will be evaluated for clinical assessment based on following outcome measures:
Primary outcome measures
The primary outcome measures includes following:
- Time to re-epithelialization [Time Frame: 4 weeks]
- Time to re-epithelization has been considered as the duration between enrolment and the dressing spontaneously peeling off from donor site without causing pain and the wounds completely closed, without fluid leakage and able to be exposed to the environment without pain. Percentage area of re-epithelialization on day 3, 7, 14, and 28, will be assessed via Bates- Jenson wound assessment tool.
- Incidence of wound infection [Time Frame: 4 weeks]
- Incidence of adverse reactions including allergic contact dermatitis (ACD) [Time Frame: 4 weeks]
Participants will be followed up until re-epithelialization of the wound. Wound assessment will be conducted daily by Research Staff blinded to treatment allocation, after complete removal of the dressing. Donor sites and wounds will be inspected for occurrence of clinical signs of infection, including excessive erythema, edema, pain, purulence, and lymphadenitis (tissue biopsies for microbiologic evaluation would be planned in the event of clinical signs of infection) until re-epithelialization.
Secondary outcome measures
The secondary outcome measures include
- 1. Dressing adherence (score) (time frame: 10 days)
- Adherence will be scored using the following scale:
- Adherence of dressing to the wound bed:
- 1 = “none” (no adherence);
- 2 = “minimal” (adherence to <25% of wound bed);
- 3 = “moderate” (adherence to 26–75% of the wound bed;
- 4 = “firm” (adherence to >75% of wound bed).
- 2. Pain during dressing changes (score) (time frame: 2 weeks)
- Participant-reported pain during removal of dressing will be evaluated using a visual analogue scale (VAS) of 0–10.
- 3. Any systemic effect after treatment
- CBC, blood glucose, electrolyte, hepatic and renal function will be analyzed to find any changes (baseline and day 28).
- 4. Incidence of Blistering (time frame: 0–6 days)
Photo documentation will be evaluated in a blinded manner by Research Staff.
Sample size for the study has been computed to detect difference in mean time to heal donor site raw area between the control site and the intervention site in the same participant assuming Mean ± SD time to heal the control side = 17 ± 4 days and Mean ±SD time to heal the intervention side = 14 ± 4 days with 95%Confidence interval and 90%Power.38 sites are required in each of the two arms, that is, 38 participants with two sites per participant. Assuming 30% to be drop out the sample size of 50 participants has been considered for the study.
Participants will be screened for the need of STSG and dressings for superficial external wounds as per criteria mentioned and participants meeting inclusion criteria will be enrolled for the trial and thereafter followed up in OPD for next 28 days. If there will be more than or equal to 80% compliance, the participant will be continued in the trial. The compliance will be assessed at each visit during the follow up.
Phase 1 study
In phase 1 of trial, after antiseptic precautions, two parallel strips of skin will be harvested from the same anterolateral aspect of thigh using the same dermatome by the same surgeon, of equal width and standard thickness between 0.20 and 0.30 mm. One donor site will receive the topical application of C1 oil prior to the standard dressing with paraffin gauzes; the control site will receive saline application. Any concomitant treatment (medications, wound care) will be thoroughly documented for the duration of the study.
Phase 2 study
Participants with superficial external wounds requiring dressing will be recruited in phase 2 of the study. Test site will receive C1 oil-impregnated dressings whereas saline will be applied at the control site. The dressings will be changed after every 24 h or earlier in case of soakage or accidental removal. Participants will be followed up on outpatient basis.
Follow up will be done on 3rd, 7th, 10th, 14th, and 28th day during both the phases of study.
Participant compliance monitoring
Participant compliance has also been monitored by personal contact, telephonic conversation/ electronic communication.
Discontinuation of study
If the study would be prematurely terminated or suspended, the investigators would promptly inform the sponsor and the IEC(s) of the termination or suspension and the reason(s) for the termination or suspension. Further, as far as possible each individual participant should undergo a complete final examination or at least a final telephone interview.
Prior and concomitant medication
Before enrolment it will be ensured that no participant is taking any medications as mentioned under exclusion criteria. In case of other illness, the participant will be allowed to take the medications as per the need and it will be noted in CRF and respective form.
To alleviate any emergency, the use of rescue medication will be permitted as per the wisdom / discretion of the Principal Investigator. However, the same will be documented in appropriate column in the Case Record Form.
Confidentiality of the participants
The participants will be informed by the investigator that all trial results recorded will be treated in strict confidence. During documentation and analysis of the trial, the individual participant will identified by their participant number, whereas the name of the participant and any personal data will be considered under data protection regulations.
Source data included all, original records of clinical findings observations, case report forms (CRF), laboratory investigations report and any other relevant document.
The original records of participants will be maintained at the study site and the photocopy of the same will be sent to the CCRAS headquarters on completion of study.
Study management at site
The centre will be responsible for setting up an information system to keep track of all participants screened, enrolled and maintained a filing system to keep all study records, study protocol, related documentation and medicine distribution records. Site visits will be made by the concerned officers from CCRAS Headquarter New Delhi.
The quantitative data will be compared using Student’s t test and the qualitative data using chi-square test.
This study will be monitored periodically by the concerned officers of the CCRAS. The investigator will provide access to all the study-related documents and study-related facilities (e.g. pharmacy, diagnostic laboratory, etc.).
The study will be conducted according to the prevalent standards of Good Clinical Practice. The Institutional Ethics Committee of the AIIMS, New Delhi approved the study protocol.
The Investigator has to meet the study requirements as specified in the protocol. Protocol amendments will be possible only in exceptional cases (e.g. where the health or well-being of the participant is affected) and only after obtaining approval from the IEC.
All participants for this study will be provided sufficient information to make decision about their participation in this study. Written informed consent will be obtained from the study participants before enrollment.
| Discussion|| |
The healing of wound is a natural phenomenon, but the natural way of healing may lack quality, promptness and aesthetics. Wound healing continues to pose challenge in the clinical field despite numerous scientific developments. Appropriate and efficient wound management is very essential. Different wounds require dressings for different reasons. Some wounds need protection from exogenous infection, whereas others need a conducive environment for healing till the skin regenerates. Accelerated re-epithelialization, minimizing pain and preventing infection are main goals of wound care. Conventional paraffin gauze dressings are inexpensive but do not contain any active agent that can promote wound healing. Thus, the quest for finding newer and better alternatives is a continuous endeavor in medical research. Further emphasis is essentially required toward new and alternative therapeutic approaches and development of technologies for wound healing. Classical Ayurvedic texts are a testament to the fact that herbal medicines have served as wound healers since ages. In various classical Ayurvedic texts about 24 metals and minerals, 164 medicinal plants and 18 animal products are described as having wound healing activity under the term Vranaropaka. Due to applicability and safety, Traditional Indian medicines have been routinely utilized for wound management and repair but scientific evidence for their wound healing potentials are very few., Some Ayurveda herbs have been screened scientifically for the evaluation of their wound healing activity in different clinical settings, but the potential of most remains unexplored.,,
Financial support and sponsorship
This study is supported by Central Council for Research in Ayurvedic Sciences (CCRAS), Ministry of Ayush, Government of India, New Delhi.
Conflicts of interest
There are no conflicts of interest.
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