Clinical trial NCT06993740: Effect of Dexmedetomidine on Microsurgery Reconstruction in Cancer Patient
Official title: The Effect of Dexmedetomidine Administration on the Success of Reconstructive Microsurgery in Cancer Patients: A Study of Glycocalyx Integrity, Inflammatory Response, Thrombosis, Angiogenesis, Oxidative Stress, and Tissue Microcirculation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Flap Monitoring
Inflammation
Thrombosis
Oxidative Stress
Glycocalyx
Anesthesia
Surgery
Flap Ischemia
Flap Necrosis
Flap Failure Risk Factors
Microsurgery
Keywords: SOD-1
IL-6
IL-10
VEGF
Syndecan-1
Dexmedetomidine
SDF
PAI-1
Flap Failure
Flap Salvage
Lead sponsor: Dharmais National Cancer Center Hospital
Sponsor class: OTHER_GOV
First posted: 2025-05-29
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the impact of perioperative dexmedetomidine administration on the success of microsurgical reconstruction in cancer patients. The intervention group will receive dexmedetomidine infusion during surgery, while the control group will receive a placebo. The study focuses on assessing surgical outcomes, particularly flap survival, alongside biochemical and histological markers related to endothelial glycocalyx integrity, inflammatory response, thrombosis, angiogenesis, oxidative stress, and microcirculatory function.
Primary purpose: TREATMENT

Brief summary: This double-blinded randomized controlled trial aims to investigate the effect of intraoperative dexmedetomidine administration on early flap viability and microvascular integrity in cancer patients undergoing elective microvascular reconstructive surgery. The primary outcome is clinical flap viability within 48 hours postoperatively, assessed using a standardized scoring system based on flap color, temperature, capillary refill time, and tissue turgor. Secondary outcomes include the evaluation of biomarkers related to endothelial glycocalyx degradation (syndecan-1), oxidative stress (SOD-1), inflammation (IL-6, IL-10), thrombosis (PAI-1), and angiogenesis (VEGF), as well as microcirculatory assessment using Sidestream Dark Field (SDF) imaging. The study is designed to determine whether dexmedetomidine improves early surgical outcomes by modulating pathophysiological processes involved in microvascular flap success.

Detailed description: Microvascular reconstructive surgery is commonly performed in cancer patients following tumor excision to restore both form and function. However, flap failure remains a major postoperative complication, particularly in oncologic patients who are more susceptible to inflammation, endothelial injury, thrombosis, and impaired tissue perfusion. Recent evidence suggests that anesthetic agents may play a role in modulating microvascular and endothelial responses during surgery, providing opportunities to enhance surgical outcomes.

Dexmedetomidine is a selective alpha-2 adrenergic receptor agonist known for its sedative, analgesic, sympatholytic, and anti-inflammatory properties. In addition to its hemodynamic stability profile, dexmedetomidine has demonstrated protective effects on the endothelium and glycocalyx, along with potential benefits in preserving tissue perfusion and reducing inflammatory and thrombotic responses. However, its clinical impact on microvascular flap outcomes in cancer patients undergoing reconstructive surgery has not been well established.

This study is a double-blinded randomized controlled trial involving 60 adult cancer patients (aged 18 to 65 years) undergoing elective microvascular reconstructive surgery. Participants will be randomized into two groups: an intervention group receiving intravenous dexmedetomidine, and a control group receiving normal saline. Both infusions will be prepared in identical syringes to maintain allocation concealment.

The primary outcome of this study is flap viability within the first 48 hours postoperatively, assessed using a standardized clinical scoring system. This scoring incorporates four key parameters: flap color, surface temperature, capillary refill time, and tissue turgor. Each parameter is evaluated to provide an integrated assessment of early microvascular flap function.

The secondary outcomes include exploratory analysis of biological processes related to microvascular integrity and function. These outcomes include the evaluation of biomarkers indicative of endothelial glycocalyx degradation (syndecan-1), oxidative stress (SOD-1), inflammatory activity (IL-6 and IL-10), prothrombotic state (PAI-1), and angiogenesis (VEGF). These markers will be analyzed from plasma and/or flap tissue at defined perioperative time points to better understand the physiological impact of dexmedetomidine.

Furthermore, real-time assessment of tissue microcirculation will be performed using Sidestream Dark Field (SDF) imaging, a non-invasive technique that enables visualization of capillary density and flow quality in the reconstructed flap area. This provides an objective and dynamic measure of tissue-level perfusion and complements the clinical viability scoring.

All patients will undergo general anesthesia induced with fentanyl 2 µg/kg and propofol 1-2 mg/kg. In the intervention group, dexmedetomidine will be administered with a loading dose of 1 µg/kg over 10 minutes, followed by a continuous infusion at 0.4 µg/kg/hour until 48 hours after surgery. The control group will receive a matched volume of normal saline according to the same timeline.

This study is expected to provide new insights into the role of dexmedetomidine in enhancing microvascular outcomes in cancer patients undergoing reconstructive surgery, potentially offering a simple yet impactful strategy to improve flap success and postoperative recovery.

Eligibility criteria: Inclusion Criteria:

1. Adult patients (aged 18-65 years) diagnosed with cancer who are scheduled to undergo microsurgical flap reconstruction.
2. Patients within the age range of 18 to 65 years at the time of enrollment.
3. Patients who provide written informed consent to participate in the study.

Exclusion Criteria:

1. Patients with a history of uncontrolled diabetes mellitus.
2. Patients diagnosed with chronic kidney disease.
3. Patients with known liver failure.
4. Patients receiving corticosteroid therapy prior to surgery.
5. Patients with uncontrolled hypertension.
6. Patients with a history of chemotherapy or radiotherapy prior to surgery.
7. Patients diagnosed with preoperative sepsis.
8. Patients requiring perioperative vasopressor support.
9. Patients with a history of prior surgery in the same operative field.
10. Patients who decline to participate in the study.

Primary outcomes:
measure: Flap Viability Score
timeFrame: 48 hours postoperatively
Secondary outcomes:
measure: Tissue Syndecan-1 Expression
timeFrame: Intraoperative tissue sampling
measure: Tissue Superoxide Dismutase 1 (SOD1) Expression
timeFrame: Intraoperative tissue sampling
measure: Interleukin-6 (IL-6) Level
timeFrame: Baseline (preoperative) and 12 hours postoperatively
measure: Interleukin-10 (IL-10) Level
timeFrame: Baseline (preoperative) and 12 hours postoperatively
measure: Vascular Endothelial Growth Factor (VEGF) Level
timeFrame: Baseline (preoperative) and 12 hours postoperatively
measure: Plasminogen Activator Inhibitor-1 (PAI-1) Level
timeFrame: Baseline (preoperative) and 12 hours postoperatively
measure: Microcirculation Assessment Using Sidestream Dark Field (SDF) Imaging
timeFrame: Immediate postoperative (sublingual site), 12 hours postoperative (flap tissue), and 48 hours postoperative (flap tissue)
Other outcomes:
Locations:
city: Jakarta
country: Indonesia
facility: Dharmais National Cancer Center Hospital
state: DKI Jakarta
city: Jakarta
country: Indonesia
facility: Dharmais National Cancer Center Hospital
state: DKI Jakarta
Study officials:
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