A multicenter, randomized, double-blind, active-control phase III clinical trial of WOXheal® [Diperoxochloric acid] topical solution in the treatment of chronic venous leg ulcer – in comparison with the active-control 0.9% sodium chloride topical solution in addition to standard of care.
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Enrollment
- 204
- Locations
- 13
- Primary Endpoint
- The primary objective of this study is to evaluate the efficacy of Diperoxochloric acid topical solution in addition to standard of care causing complete wound closure or reduction in wound surface area in the chronic venous leg ulcers in comparison with active control 0.9% sodium chloride topical solution in addition to standard of care on the basis of primary, secondary and tertiary endpoints.
Study Overview
Brief Summary
Diperoxochloric acid topical solution isapproved by CDSCO in the indication of diabetic neuropathic foot ulcer of skinand subcutaneous tissue. From the data available from phase II and phase III clinicaltrial, DPOCL caused faster healing of the ulcer when compared to active-controltreatment in terms of week wise percentage reduction in wound surface area. Itwas also observed that certain clinicians successfully used WOXheal[Diperoxochloric acid] topical solution off-label in the treatment ofnon-healing venous leg ulcers, decubitus ulcers [pressure ulcers] as well asother non-healing ulcers caused by collagen vascular disease.Therefore, this clinical trial is planned toinvestigate efficacy and safety of WOXheal [Diperoxochloric acid] topicalsolutionin the treatment ofvenous leg ulcers in addition to standard care of treatment.
Study design:
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Diperoxochloricacid topical solution is approved by CDSCO in the indication of diabetic neuropathicfoot ulcer of skin and subcutaneous tissue7. This clinical trial isplanned as part of approval of Diperoxochloric acid topical solution in theadditional indication of chronic venous leg ulcers based on this new phase IIIrandomized clinical trial in compliance with New Drug and CT rules, March 19,2019 [GSR 227E].
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Itwill be a prospective, double-blind, multi-centered, randomized, active-control,comparative phase III clinical trial to test the efficacy and safety ofDiperoxochloric Acid [DPOCL] topical solution in patients with chronic venousleg ulcers in addition to standard of care vis-Ã -vis isotonic normal salinesolution.
3.Thestudy will be conducted in the hospital setup, with number of patients not lessthan 204, i.e. at least 102 in the Test arm and 102 in the Active-control armfor a statistically evaluable 84 patients in each arm. The patients could betreated on outpatient [OP] basis or may be in need of in-patient admission[IP]. The sample size estimation is described in section 17.1 of this protocol.
4.Adetailed medical history will be obtained from all enrolled Patients, whichwill be followed by thorough clinical examination.
5. Followingthe screening procedure as part of this trial, the eligibility of the patientto participate in the trial would be decided by the investigator based on theinclusion-exclusion criteria described in the protocol.
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Depending on the size of the dressing [5×5 or 5×10or 10×10 or as per investigator’s discretiondepending on wound surface area],one or two or more units of investigational product will be provided to the Patientat each visit by the investigator at no cost. Since the trial has double-blindstudy design, the patient or the investigator would not know the identity ofinvestigational product [Test or active-control].
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Totalduration of the clinical trial for any patient who is randomized and enrolled willbe maximum of 12 weeks. The trial could end prior to week 12 for an individualpatient, if complete wound closure is achieved earlier. On the other hand, theinvestigator could switch the patient on alternative treatment modality, ifthere is no satisfactory response observed from the treatment. However, fromthe enrolment in the study on day 0, the patient must complete at least 4weeks, to qualify him/ her for the decision of switching to alternativetreatment modality due to unsatisfactory treatment response. This will not beconsidered as adverse event.
8. Patientswill be instructed to prepare the reconstituted solution (ready to usesolution) as per the instructions given below.
Open‘Bottle A’ and ‘Bottle B’.
Pourthe contents of Bottle A in to Bottle B.
Closethe bottle B with bottle cap.
Mix the content by gently moving the bottleupside down for 5 times.
9.Patientswill be asked to use the reconstituted solution within 14 days once it isprepared. Reconstituted solution should not be used after 14 days of mixing/reconstitution.
10.Patientwill be instructed to use the reconstituted solution as per the instructionsgiven below:
Washhands thoroughly before applying DPOCL topical solution.
Takeout the dropper from the plastic bag (provided in the pack) and fill it on thebottle B.
Apply3.5 mL of this solution with help of the dropper on the 5 x 5 cm dressing (innergauze) to bring the dressing to earth moist conditions. As per size of thedressing, the dose would vary, i.e. for 5 x 10 cm dressing (inner gauze), 7 mLsolution would be needed, whereas for 10 x 10 cm dressing (inner gauze), 14 mLsolution would be needed. Similarly, for 4 x 4 cm dressing (inner gauze), 2.5mL solution would be needed.
Do nottouch dropper to the dressing or gauze.
Thenapply this inner gauze on the wound.
Coverthis inner gauze with outer gauze which will prevent the wound area fromrunning dry.
Fixthe gauze in position by rolling the bandage over the gauze and secure the endsby the microtape.
Dailyremove the outer bandage and apply investigational product on inner bandagewithout removing the inner bandage form the wound.
Changethe outer gauze daily and inner gauze on every alternate day.
10. Patientswill be instructed to keep a note of daily symptoms and inform theinvestigator.
- Incase of adverse event/ serious adverse event irrespective of whether it is dueto study procedure or study drug and anytime within 12 weeks from theenrolment, the investigator could withdraw the patient and switch toappropriate medical or surgical management of the said AE/ SAE.
12. Allthe patients will be asked to revisit the clinical trial center for efficacyand safety assessment on day 7, day 14, day 28, day 42, day 56, day 70 and day84. For each visit, a grace period of ± 3 days will be given to patients andwill not be considered as protocol deviation.
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If theCWC is achieved prior to scheduled visit, it is acceptable to ask the patientto visit the clinical trial site for evaluation of CWC. Alternatively, if thepatient experiences any AE or SAE, he/ she could visit the clinical trial sitebefore the scheduled visit.
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Incase the CWC is achieved prior to scheduled day of visit, the patient couldcome to the hospital and procedures related to end-of-study [EOS] andpost-study safety assessment would be done. This, again would not be consideredas protocol deviation.
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If thewound is not completely healed at the end of the trial (Day 84) then it will bedecided by the investigator whether the treatment is needed and should becontinued until CWC. In this case the patient would be provided with investigationalproduct after opening the blind.
Study Design
- Study Type
- Interventional
- Allocation
- Computer generated randomization
- Masking
- Participant and Investigator Blinded
Eligibility Criteria
- Ages
- 18.00 Year(s) to 80.00 Year(s) (—)
Inclusion Criteria
- •1.Age: > 18 to ≤ 80 years.
- •2.Gender: Male or female 3.All the patients willing to voluntarily participate in the clinical trial and signing on duly filled Informed Consent Form.
- •4.Patients with at least one or maximum 3 difficult-to-heal varicose or post-thrombotic venous leg ulcer on standard care (appropriate compression system) localized between the knee and ankle, including the perimalleolar area.
- •5.Venous insufficiency confirmed by a venous Doppler/ duplex ultrasound scan.
- •A previous scan done within 6 months before randomization can be used.
- •If there is no previous adequate scanning, a new scanning has to be performed before randomization.
- •6.The target ulcer area should be > 4cm2 and ≤ 40 cm2 calculated by largest length × largest width with less than 50% of necrotic tissue.
- •7.Ulcer duration ≥2 months and ≤3 years.
- •8.Target ulcer classification using WIFI grade: Wound 1 or 2, Ischemia 1 or 2, foot infection 1 or 2.
Exclusion Criteria
- •1.Patients with more than 3 ulcers in a single extremity.
- •2.Patients with ulcers measuring wound surface area more than 40 cm2 and deep ulcerations with bone or tendon exposure, or uncontrolled infection.
- •3.Patients who have excessive tissue necrosis that is unlikely to benefit from medication, or those Patients who, in the opinion of the Investigator, are felt likely to require revascularization within 1 month of screening.
- •4.Patients with severe limb ischemia.
- •5.Patients who are considered likely to require a major amputation (at or above the ankle) within 3 months of screening.
- •6.Patients who have had a technically successful revascularization by surgery or angioplasty within 2 months.
- •If Patients are more than two months from revascularization and still meet the inclusion criteria, they may be considered for enrollment.
- •Patients who have had a technically unsuccessful attempt at revascularization may be enrolled at least one week from the procedure.
- •7.Treatment of foot ulcers with growth factors, stem cells or equivalent medication within the 8 weeks prior to screening.
- •8.Patients having progressive weight loss, i.e. ≥ 20% within last 3 months prior to enrollment in the trial.
- •9.Poor nutritional status albumin < 2.5 g/dL or total protein < 4.5 g/dL.
- •10.Treatment with corticosteroids, immunosuppressive or chemotherapeutic/ cytotoxic agents, radiotherapy – either ongoing or within 60 days prior to enrolment in the trial.
- •11.Other diseases, which can alter the course of ulcer such as connective tissue disease, renal failure (serum creatinine > 3mg /dL) liver failure, malignancy.
- •12.Pregnant or nursing mothers.
- •13.Mentally or neurologically disabled Patients that are considered not fit to approve their participation in the study.
Outcomes
Primary Outcomes
The primary objective of this study is to evaluate the efficacy of Diperoxochloric acid topical solution in addition to standard of care causing complete wound closure or reduction in wound surface area in the chronic venous leg ulcers in comparison with active control 0.9% sodium chloride topical solution in addition to standard of care on the basis of primary, secondary and tertiary endpoints.
Time Frame: Seven [7] visits are planned in this study: | 1.Visit 0 will be the baseline on day 0 before first treatment by Test or Active-control medication, followed by | 2.Visit 1: day 7, | 3.Visit 2: day 14, | 4.Visit 3: day 28, | 5.Visit 4: day 42, | 6.Visit 5: day 56 | 7.Visit 6: day 70 and | 8.Visit 7: day 84 | For each visit, a grace period of ± 3 days will be given to patients and will not be considered as protocol deviation.
Secondary Outcomes
- The secondary objective of this study is to evaluate the safety of Diperoxochloric acid topical solution in addition to standard of care in comparison with active control 0.9% sodium chloride topical solution in addition to standard of care by comparing treatment-emergent adverse events or serious adverse events as well as comparison of baseline and end-of-study assessment by virtue of physical examination and clinical laboratory investigations(Seven [7] visits are planned in this study:)