Enhancing Wound Perfusion in High-Risk Lower Extremity Orthopaedic Surgery: A Study on Nitropaste Using Intraoperative SPY Imaging.

Phase 1

Not yet recruiting

• Conditions: Achilles Tendon Repairs/Reconstructions; Pilon Fracture of Tibia; Tibial Plateau Fracture; Ankle Fracture (Bimalleolar Equivalent, Bimalleolar, or Trimalleolar); Calcaneus Fractures; Talus Fracture; Wound Infection Deep; Wound Infection Post-Traumatic; Wound Dehiscence, Surgical
• Interventions: Drug: Nitroglycerin Ointment 2%

• Registration Number: NCT07004764
• Lead Sponsor: Johns Hopkins University

Brief Summary

Enhancing Wound Perfusion in High-Risk Lower Extremity Orthopaedic Surgery: A Feasibility Study on Nitropaste Using Intraoperative SPY Imaging.

Detailed Description

Tissue perfusion is a critical determinant of wound healing, particularly in lower extremity surgery where wound necrosis, dehiscence, and infection can result in limb loss. Despite current advances in wound therapy, rates of wound complications for certain lower extremity incisions remain high. Thus, there remains a critical need to identify agents that may potentially augment wound healing in orthopaedic surgery.

Nitropaste has been successfully used in plastic surgery to enhance perfusion and reduce flap necrosis, but its role in orthopaedic surgery is under-explored. In a meta-analysis of 6947 patients from 3 randomized controlled trials (RCTs) and 2 retrospective studies found that the use of nitropaste was associated with 0.23 odds \[0.10-0.53, 95% confidence interval\] of reduced mastectomy flap failure. Preliminary data from the investigator's institution involving 18 patients who received intraoperative nitropaste showed no adverse hypotensive effects, though wound complications occurred in three cases. Laser Assisted Indocyanine Green (LA-ICG) provides real-time, quantitative perfusion measurements, making it an ideal tool to evaluate the efficacy of nitropaste. Therefore, The purpose of this study is to evaluate the effects of nitropaste on immediate tissue perfusion and wound complications in high-risk lower extremity orthopaedic incisions using LA-ICG. Additionally, the investigators will assess the safety of single-dose nitropaste in these patients. The investigators hypothesize that intraoperative nitropaste application will significantly improve tissue perfusion, which in turn would be associated with reduced wound complications, with minimal adverse effects.

Aim 1: To evaluate the effect of nitropaste on immediate tissue perfusion in lower extremity orthopaedic incisions using LA-ICG.

1. Primary outcomes: Relative fluorescence unit (RFU), absolute fluorescence units (AFU), mean incision perfusion (MIP), and mean perfusion impairment (MPI)

2. Null hypothesis: The investigators hypothesize that nitropaste would not be associated with a significant increase in perfusion, as measured by RFU, AFU, MIP and MPI.

Aim 2: To assess trial feasibility and ability to identify wound complications for a future large-scale trial.

1. Primary outcomes: Recruitment rate, retention rate, and wound complications, which include wound dehiscence, wound necrosis, superficial infection, and deep infection.

2. Recruitment goal: 50% recruitment at 8 months

3. Retention rate goal: 80% of patients with minimum of 3 months follow-up at trial conclusion

4. No a priori hypotheses.

Aim 3: To assess the safety of nitropaste in lower extremity orthopaedic surgeries.

1. Secondary outcomes: Hypotension, headache, dizziness, allergic reactions, and other adverse events.

2. No a priori hypotheses.

Study Timeline

• Status Verified: 2025-05
• Study First Submitted: 2025-05-27
• Study First Submitted QC: 2025-05-27
• Last Update Submitted: 2025-05-27
• Study First Posted: 2025-06-04
• Last Update Posted: 2025-06-04
• Study Start: 2025-08
• Primary Completion: 2026-07
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• Adults aged 18 years or older.

• Undergoing surgery for one of the following procedures:

  • Current Procedural Terminology (CPT) 28415 - Open reduction calcaneal fracture ± internal/external fixation
  • CPT-27814 - Open reduction of bimalleolar fracture ± internal/external fixation
  • CPT-27822 - Open reduction trimalleolar ankle fracture, medial and lateral malleoli only, ± internal/external fix
  • CPT-27823 - Open reduction trimalleolar ankle fracture, including posterior malleolus, ± internal/external fix
  • CPT-27826 - Open reduction pilon fracture, internal/external fixation of fibula ONLY
  • CPT-27827 - Open reduction pilon fracture, internal/external fixation of tibia ONLY
  • CPT-27828 - Open reduction pilon fracture, internal/external fixation of tibia AND fibula
  • CPT-27535 - Open reduction unicondylar tibial plateau fracture, ± internal/external fixation
  • CPT-27536 - Open reduction bicondylar tibial plateau fracture, ± internal/external fixation
  • CPT-28445 - Open reduction of talus fracture, ± internal/external fixation
  • CPT-27650 - Primary Achilles tendon repair

• English-speaking

• Able to provide informed consent during preoperative clinic visit, in the preoperative nursing area, or on inpatient units.

Exclusion Criteria

• Contraindications to nitroglycerin, including known allergy.
• Allergy to indocyanine green or components of ICG dye, including allergies to iodine or shell-fish.
• Severe kidney injury, as determined by attending surgeon and/or anesthesiologist, that would impair clearance of ICG dye.
• Pregnant patients

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nitropaste	Nitroglycerin Ointment 2%	All patients enrolled in this study will receive a baseline perfusion measurement with the LA-ICG system. This will occur after wound closure. Subsequently, all patients will receive a single dose of nitropaste intraoperatively and a final LA-ICG tissue perfusion measurement.

Primary Outcome Measures

Name	Time	Method
Absolute fluorescence unit (AFU)	Intraoperative measurement	raw fluorescence measurement
mean incision perfusion (MIP)	Intraoperative measurement	the mean fluorescence of 10 points adjacent to the incision.
mean perfusion impairment (MPI)	Intraoperative measurement	the difference between mean of each pair of points on each side of the incision.
Relative fluorescence unit (RFU)	Intraoperative measurement	Will be calculated as a ratio of the mean fluorescence measure to the mean "normal" measurement. The mean "normal" measurement will be defined as the maximal signal intensity in a region outside of the wound area.

Secondary Outcome Measures

Name	Time	Method
Number of participants with Deep infection	From surgery to 3 months post-operation	Any wound infection that requires surgical management
Number of participants with Superficial infection	From surgery to 3 months post-operation	participants with any wound infection that is treated only with oral antibiotics
Number of Participants with Wound dehiscence	From surgery to 3 months post-operation	participants with wound dehiscence (when two edges of a wound separate)
Number of participants with Wound necrosis	From surgery to 3 months post-operation	participants with any death of peri-incisional skin

Trial Locations

Locations (2)

The Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

Johns Hopkins Bayview Medical Center; 🇺🇸 Baltimore, Maryland, United States