Trial Outcomes & Findings for N-Acetyl-Cysteine (NAC) for Healing of Amputation Stumps in the Setting of Diabetes (NCT NCT03253328)

Recruited from March 2017 to April 2020. We initially planned to enroll 15 subjects in each group but recruitment was suspended in May 2020 due to COVID-19. Study team leadership determined that unmasking of study randomization would facilitate analysis of primary/secondary endpoints and determine whether data supported overall study hypothesis. After pandemic disruptions were eased interim study analysis was completed and the study closed. No safety concerns led to early termination.

Race and Ethnicity were not collected from any participant.

Images were collected from the SPY Elite LAFA apparatus. Regions of interest were drawn in a standardized fashion around either the incision or the whole amputation stump. NIH image J software was used to evaluate peak perfusion signal intensity in all regions of interest. Change in LAFA was assessed at postoperative day (POD) 0, 3, and 5. Fold change in % perfusion in the ROI's between POD 0/3/5 was determined and compared between study groups. The primary outcomes were change in postoperative Laser-Assisted Fluorescent Angiography (LAFA) perfusion at POD3 and POD5 and stump healing at postoperative day 30 (POD30).

Amputation stump photographs were serially obtained for all study patients immediately before LAFA assessments on POD 0, 3, and 5. A blinded observer evaluated amputation stump incision healing using a modified Bates-Jensen Score (mBJS) wound assessment tool. As previously described, the amputation stumps were evaluated on the following criteria: amputation stump skin color, epithelialization, amount of exudate, and the presence and volume of eschar. Each wound healing characteristic was given a score of 1 to 5, with higher scores indicating worse healing. Eschar volume was determined using ImageJ software. Aggregate mBJS scores were derived for both the whole stump and along the suture line. Clinical amputation stump healing was determined by the surgeon at follow-up clinical evaluations up until POD30. De Silva GS, Saffaf K, Sanchez LA, et al. Amputation stump perfusion is predictive of post-operative necrotic eschar formation. Am J Surg. 2018;216:540-546.

POD0 LAFA was evaluated for all patients and patients that demonstrated amputation stump peak perfusion defects were considered high risk. Within these patients we then evaluated amputation stump perfusion at POD5. Change in perfusion over this time was compared between the study groups.