N-Acetyl-Cysteine (NAC) for Healing of Amputation Stumps in the Setting of Diabetes

NCT ID: NCT03253328

Last Updated: 2024-08-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-01
• Study Completion Date: 2022-06-27

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.

Conditions

Diabetes Mellitus; Critical Limb Ischemia; Lower Limb Amputation Knee; Peripheral Arterial Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active Arm N-acetyl cysteine (NAC)

Upon study enrollment, patients will be randomized 1:1 by Investigational Pharmacy to a standard adult intravenous dose of NAC (1200mg twice a day) for 6 days post-amputation.

Group Type: ACTIVE_COMPARATOR

Active Arm N-acetyl cysteine (NAC)

Intervention Type: DRUG

N-acetyl cysteine (NAC) 1200mg twice a day for 6 days post-amputation

Placebo Arm

Upon study enrollment, patients will be randomized 1:1 by Investigational Pharmacy to placebo ½ normal saline infusion (twice a day) for 6 days post-amputation.

Group Type: PLACEBO_COMPARATOR

Placebo Arm

Intervention Type: DRUG

Placebo 1/2 normal saline infusion twice a day for 6 days post-amputation

Interventions

Active Arm N-acetyl cysteine (NAC)

N-acetyl cysteine (NAC) 1200mg twice a day for 6 days post-amputation

Intervention Type: DRUG

Placebo Arm

Placebo 1/2 normal saline infusion twice a day for 6 days post-amputation

Intervention Type: DRUG

Other Intervention Names

N-acetyl cysteine (NAC); Placebo 1/2 normal saline infusion

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).

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mohamed Zayed, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 35129469 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

201611065

Identifier Type: -

Identifier Source: org_study_id