Clinical trial NCT03253328: N-Acetyl-Cysteine (NAC) for Healing of Amputation Stumps in the Setting of Diabetes
Official title: N-Acetyl-Cysteine for Healing of Amputation Stumps in the Setting of Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Diabetes Mellitus
Critical Limb Ischemia
Lower Limb Amputation Knee
Peripheral Arterial Disease
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2017-08-17
Enrollment: 33
Sex: ALL
Minimum age (years): 30
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this pilot clinical study the investigators propose to conduct a prospective, randomized, double-blinded, placebo-controlled clinical trial for 30 days for participants with critical limb ischemia (CLI) who undergo a major (above-knee or below-knee) lower extremity amputation. By exploring the primary endpoints we aim to determine whether NAC can affect amputation stump perfusion and healing. Based on preclinical data, the investigators hypothesize that NAC will augment both amputation stump perfusion as well as healing. The investigators will utilize the data from this trial to determine the true effect size that is necessary for a larger clinical trial to determine the clinical efficacy of NAC is healing surgical sites such as major lower extremity amputation stumps.

Detailed description: In this pilot clinical study the investigators propose to conduct a prospective, randomized, double-blinded, placebo-controlled clinical trial, in 50 participants with CLI who have undergone a major (above-knee or below-knee) lower extremity amputation. 25 participants will receive NAC 1200mg intravenously twice a day for 6 consecutive days following amputation. 25 participants will receive placebo saline intravenous infusion twice a day for 6 days following amputation. Post-amputation participants will be monitored for specific anthropometric parameters and stump perfusion assessments (using laser-assisted fluorescent angiography and transcutaneous oxygen pressure measurement). The primary study endpoints are to determine if lower extremity stump healing and perfusion are affected by perioperative NAC administration. A secondary endpoint will be to determine the effect size that would be necessary to power a larger clinical trial to determine whether NAC treatment can affect tissue perfusion and healing at major lower extremity amputation stumps in participants with CLI.

Eligibility criteria: Inclusion Criteria:

* Subject undergoing elective major (above-knee or below-knee) lower extremity amputation for CLI
* Both male and female patients
* All ethnic groups
* Between of the ages of 30-90 years old
* Adequate nutritional status - defined as BMI \> 19

Exclusion Criteria:

* Pregnant women, and women who are breastfeeding
* Known history of end-stage liver disease
* Severe asthma
* Heavy alcohol consumption (male \> 2 drinks per day and women \> 1 drink per day)
* Individuals actively receiving chemotherapy.
* Anticipated enrollment in another study that investigates another drug agent within 30 days from enrollment in this study.
* Patients receiving carbamazepine.
* Severe anemia (HCT \< 22).
* Allergy to either NAC or Indocyanine Green (ICG).
* Patients with open wound(s) from a prior amputation on the ipsilateral limb (excluding patients who had prior partial foot amputation, who are now requiring a below-knee or above-knee amputation).

Primary outcomes:
measure: Change in Postoperative Laser-Assisted Fluorescent Angiography (LAFA) Perfusion.
timeFrame: Day 0, Day 3, Day 5
measure: Stump Healing Assessment at Postoperative Day (POD) 30.
timeFrame: 30 days
Secondary outcomes:
measure: Amputation Stump Perfusion in High Risk Patients
timeFrame: POD5
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Mohamed Zayed, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lee JV, Engel C, Tay S, DeSilva G, Desai K, Cashin J, Semenkovich CF, Zayed MA. Impact of N-Acetyl-Cysteine on Ischemic Stumps Following Major Lower Extremity Amputation: A Pilot Randomized Clinical Trial. Ann Surg. 2022 Nov 1;276(5):e302-e310. doi: 10.1097/SLA.0000000000005389. Epub 2022 Jan 24.