|Year : 2022 | Volume
| Issue : 4 | Page : 216-219
A-heal® in the management of chronic nonhealing ulcers: A case series
Ajay Kumar, Md Qamar Azam, Nilesh Y Jagne
Department of Trauma Surgery, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
|Date of Submission||10-Aug-2022|
|Date of Decision||30-Sep-2022|
|Date of Acceptance||07-Oct-2022|
|Date of Web Publication||16-Dec-2022|
Md Qamar Azam
Department of Trauma Surgery, All India Institute of Medical Sciences, Rishikesh - 249 201, Uttarakhand
Source of Support: None, Conflict of Interest: None
Background and Objective: The aim of this study is to assess the efficacy of A-Heal® in the treatment of nonhealing ulcers (NHU). Patients and Methods: This is a case–control study involving 12 patients who applied A-Heal® 10 mg twice a day on an NHU till the complete healing of the ulcer. The control group had the standard treatment. A-Heal® is a 13 amino acid chain, which was initially isolated from the human placenta, is now synthesized, and has shown to be a powerful angiogenesis factor. Before starting the trial, morphologic features of the ulcers were noted including, size, shape, location, and associated diseases. The follow-up period was set at 6 months. Results: The average age of the treated patients was 52.5 ± 5.3 years in the study group and 51.9 ± 4.7 years in the control group. The mean duration of the ulcer was 13.7 ± 5.3 weeks. All the ulcers were located in the lower limbs. In 9 (75%) patients, there was total healing of ulcers in 22 days and three patients showed signs of wound healing with a reduction in wound size and required an additional 1 week for total healing of the ulcer. Regarding the secondary outcomes of preliminary efficacy, total healing and significant reduction of the area were observed in all patients. There were no adverse events recorded. Conclusion: This case series shows that A-Heal® has proved to be safe with a good preliminary efficacy to heal NHUs, according to the protocol and doses used. A larger clinical trial is needed to verify our results.
Keywords: A-Heal, angiogenesis factor, efficacy, nonhealing ulcer
|How to cite this article:|
Kumar A, Azam MQ, Jagne NY. A-heal® in the management of chronic nonhealing ulcers: A case series. Asian J Pharm Res Health Care 2022;14:216-9
|How to cite this URL:|
Kumar A, Azam MQ, Jagne NY. A-heal® in the management of chronic nonhealing ulcers: A case series. Asian J Pharm Res Health Care [serial online] 2022 [cited 2023 Feb 6];14:216-9. Available from: http://www.ajprhc.com/text.asp?2022/14/4/216/363941
| Introduction|| |
Ulcers which do not heal within 9 weeks are labeled as chronic nonhealing ulcers (NHU).
The reported prevalence of chronic NHU in the world ranges between 2% and 12.6%, and makes one of the leading health-care problems with 26 million people suffering in the US alone with exaggerated morbidity, and in the US alone, it cost the over $25 billion annually which significantly adds to the cost, and diabetic ulcers are responsible for up to 50% of the ulcers. The cost of managing diabetic foot ulcers is ever-increasing universally. It was estimated that the annual cost of treatment of nondiabetic foot ulcers costs $0.13 billion, whereas diabetic foot ulcer treatment costs, $1.38 billion, and in England about ≤962 million was spent in 2015.
The principle management of the NHU is to keep the ulcer clean, devoid of necrotic tissue, and treat associated conditions, which may delay healing, like diabetes mellitus (DM). Due to the failure of the healing of the NHU, a plethora of treatment modalities are in vogue. As the etiology of wounds varies, the effective therapy to treat such wounds also varies. The use of antibiotics to keep the ulcer uninfected, hyperbaric oxygen, vacuum-assisted closure, and growth factors are in use.,,
In the past 20 years, the use of growth factors, cellular therapies, and stem cell therapy took the front seat in the treatment of recalcitrant ulcers, which fail to heal with the standard therapy. The objective of the case series was to evaluate the safety and efficacy of A-Heal® in the treatment of NHU of the lower extremity.
| Patients and Methods|| |
After the approval of the institutional review board of the AIIMS, Rishekesh, wide (29712/2020) the study was done as per the guidelines of the Declaration of Helsinki, and all care was taken to maintain patient safety and confidentiality. All patients gave informed consent to be part of the study.
Twelve consecutive patients in the age group of 18-65 years who gave consent formed the study group and 12 patients were assigned to the control group. All patients in the study and control groups had unhealed ulcers in the lower limbs primarily due to trauma. Recruitment of the patients was for 4 months. The inclusion criteria were patients NHU with Wagner's Grades 1 and 2, ulcer size between 2 and 10 cm in the area, ankle-brachial index >0.75, and consent for follow-up of the study duration. Patients with uncontrolled DM, ulcers ≥11 cm, and those who refused to sign the consent were excluded.
After inclusion in the study, the ulcer was debrided and cleaned with normal saline and A-Heal 10 mg was applied twice a day on the NHU till the complete healing of the ulcer. It was applied as a thick layer and a dry sterilized nonsticking dressing was placed over the dressing and covered with a bandage. The control group of patients had the standard treatment of debridement and clean and dry dressing. The observations of the treatment were recorded after every week in both groups. Photographs were taken and the following points were recorded: type of wound discharge, purulent or seropurulent, the estimate of the quantity of wound discharge, changes in the size, granulation tissue formation as a percentage of the total surface area, and measurement of the size of wound in both the diameters.
| Results|| |
Twelve patients were recruited in the study and completed the study. The average age of the treated patients was 52.5 ± 5.3 years and 51.9 ± 4.7 years in the control group. They were all male patients. The mean duration of the ulcer was 13.7 ± 5.3 weeks. All the ulcers were located in the lower limbs and all patients had trials of standard treatment such as local and oral antibiotics, debridement, skin grafts, and dressings. Six (50%) of the ulcers were due to DM, 3 (25%) were pressure ulcers, and 3 (25%) were postarterial injury and repair. There were seven NHU of ≥2 cm and 5 <1.9 cm. The causes of ulcers in the study and control groups were similar. Within 2 weeks from the start of the treatment, small areas of granulation tissue started to appear in and around the ulcer, and a significant shrinkage in the size and increase in tissue mass was observed as a sign of healing and improvement.
In 9 (75%) patients, there was total healing of ulcers in 21.66 ± 4.61 days and three patients showed signs of wound healing with a reduction in wound size and required an additional 1 week for total healing of the ulcer [Table 1]. In the control group, there was no attempt at any healing. There were no complications related to A-Heal™. All patients were followed up for the 6-month duration and did not find any breakage of the wound, no irritation, or itching of the healed ulcers. [Figure 1], [Figure 2], [Figure 3] are the clinical pictures of pre- and posttreatment.
|Figure 2: A 25-year-old patient with postvascular repair with partially taken skin graft and unhealed ulcer and posttreatment after 16 days|
Click here to view
| Discussion|| |
This study shows that in 60% of patients, there was total healing of ulcers within 2 weeks of treatment and three patients showed signs of wound healing with a reduction in wound size and required an additional 1 week for total healing of the ulcer. Overall, there was a clear and significant reduction in ulcer size in treated patients. Second, there were no adverse effects during the treatment and follow-up period, indicating the safety and effectiveness of the treatment modality for chronic NHU.
Many causes have been attributed to the development of the NHU and many treatments have been suggested. In the past decade or so many growth factors and cellular therapies such as platelet-derived growth factor, vascular endothelial growth factor, transforming growth factor-β, insulin-like growth factor, and fibroblast growth factor came into vogue to improve wound healing., It was reported that the mechanism by which PRP acts is by platelets releasing cytokines which improves healing., Recently, stem cells in the form of mesenchymal stem cells (MSC) are being used in the healing of NHU. In many animal studies, stem cells have been shown to improve the healing of chronic ulcers. Bone marrow-derived MSC stimulated migration and angiogenesis, which increase wound healing. With the plethora of recommended treatments still, ulcers do not heal but our study has shown that in all our patients with NHU within the expected time all the ulcers healed.
Neovascularization or angiogenesis is important for wound healing as it involves the growth of new capillaries to form granulation tissue., It was logical that the local application of an angiogenesis factor would help in the healing of the ulcers. Sadat-Habdan mesenchymal stimulating peptide, which is the main component of A-Heal®, was shown in animal studies to be a potent angiogenesis factor.,, Hence, in this study, an angiogenesis factor A-Heal was used and showed remarkably good results. In conclusion, this phase I study done on 12 patients showed that in all the patients, the NHU healed with a mean of 21.66 ± 4.61 days; second, the use of A-Heal did not produce any adverse events. We believe further studies with an increased number of patients are warranted.
| Conclusion|| |
Management of NHU has been a challenge as many factors are involved in the healing of ulcers. Various modalities of treatment are available but the complete success quite apart. Our case series which is parallel to Phase I trials, we used A-Heal a natural angiogenesis factor which is now synthesized exibited potential healing strength. WE believe more larger studies are needed to further validate our results.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]