Clinical trial NCT07004764: Enhancing Wound Perfusion in High-Risk Lower Extremity Orthopaedic Surgery: A Study on Nitropaste Using Intraoperative SPY Imaging.
Official title: Enhancing Wound Perfusion in High-Risk Lower Extremity Orthopaedic Surgery: A Feasibility Study on Nitropaste Using Intraoperative SPY Imaging.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
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
Keywords: Laser-assisted indocyanine green angiography
nitropaste
nitroglycerin
topical nitroglycerin
Achilles tendon repairs/reconstructions
Pilon Fracture of Tibia
Tibial Plateau Fracture
Ankle Fracture (bimalleolar equivalent, bimalleolar, or trimalleolar)
Calcaneus Fractures
Talus fracture
Wound Dehiscence
Wound infection
tissue perfusion
Orthopaedic surgery
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Orthopaedic Trauma Association
First posted: 2025-06-04
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study is a single-arm open-label prospective clinical trial with no randomization or placebo. All patients will serve as own controls for LA-ICG fluorescence measurement. This study is considered a Phase I feasibility study, or a Stage 2a Development study under the IDEAL Framework
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Absolute fluorescence unit (AFU)
timeFrame: Intraoperative measurement
measure: Relative fluorescence unit (RFU)
timeFrame: Intraoperative measurement
measure: mean incision perfusion (MIP)
timeFrame: Intraoperative measurement
measure: mean perfusion impairment (MPI)
timeFrame: Intraoperative measurement
Secondary outcomes:
measure: Number of Participants with Wound dehiscence
timeFrame: From surgery to 3 months post-operation
measure: Number of participants with Wound necrosis
timeFrame: From surgery to 3 months post-operation
measure: Number of participants with Superficial infection
timeFrame: From surgery to 3 months post-operation
measure: Number of participants with Deep infection
timeFrame: From surgery to 3 months post-operation
Other outcomes:
measure: recruitment rate
timeFrame: From study start to final recruitment approximately 8 months
measure: retention rate
timeFrame: From study start to 3 months after final patient is recruited
Locations:
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Henry T Shu, MD
role: STUDY_DIRECTOR
affiliation: Johns Hopkins University
name: Babar Shafi, MD, MSPT
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sanniec K, Teotia S, Amirlak B. Management of Tissue Ischemia in Mastectomy Skin Flaps: Algorithm Integrating SPY Angiography and Topical Nitroglycerin. Plast Reconstr Surg Glob Open. 2016 Oct 6;4(10):e1075. doi: 10.1097/GOX.0000000000001075. eCollection 2016 Oct.