Efficacy of Cryopreserved Amniotic Membrane Allograft in the Management of Refractory Chronic Venous Leg Ulcers: A Randomized Controlled Trial

Background and aims Chronic venous leg ulcers present a clinical challenge due to persistent inflammation, proteolytic imbalance, and senescence of the extracellular matrix. Dehydrated amniotic products are utilized; however, cryopreserved amniotic membrane retains the native heavy chain hyaluronic acid and viable growth factors that are often altered during heat dehydration processing. This study evaluated the efficacy of cryopreserved amniotic membrane allografts in promoting wound closure and reducing pain in patients with refractory venous ulcers compared to standard compression therapy. Methods A prospective, single-center, randomized controlled trial was conducted. Sixty-four patients with venous ulcers persisting for more than eight weeks were randomized (1:1). The intervention group (n=32) received topical application of culture-confirmed cryopreserved amniotic membrane alongside standard multi-layer compression therapy. The control group (n=32) received standard compression therapy alone. Wounds were assessed weekly by blinded independent evaluators. The primary efficacy endpoint was the complete wound closure rate at 45 days. Secondary outcomes included Kaplan-Meier survival analysis for time-to-healing, microbiologically confirmed infection rates, and pain reduction measured by the Visual Analog Scale (VAS). All analyses were conducted on an intention-to-treat (ITT) basis. Results The intervention group achieved a higher rate of complete wound closure (81.25%) compared to the control group (46.88%) at 45 days (Risk Difference: 34.4%, 95% CI: 12.4% to 56.3%; p=0.004). Kaplan-Meier survival analysis indicated a lower median time to complete epithelialization in the intervention group (36 days, 95% CI: 31-41) versus the control group (78 days, 95% CI: 71-85) (Log-rank test, p<0.001). Patients in the intervention group reported lower VAS pain scores by day 14. The incidence of confirmed wound infection was 6.25% in the intervention group versus 28.12% in the control group (Risk Difference: 21.9%, 95% CI: 4.4% to 39.4%; p=0.02). Conclusion Cryopreserved amniotic membrane promotes wound closure and reduces pain in refractory chronic venous leg ulcers. Its application serves as a biological adjunct to standard compression therapy in the management of hard-to-heal wounds.