Imaging of Peri-operative (periOP) Lung Injury

Phase 2

Terminated

• Conditions: Acute Lung Injury; Chronic Obstructive Pulmonary Disease (COPD)
• Interventions: Radiation: SPECT-CT imaging; Drug: AxV-128/Tc; Procedure: Whipple procedure; Procedure: Major surgery

• Registration Number: NCT02978885
• Lead Sponsor: Columbia University

Brief Summary

The aim of study is to determine if 99mTc Annexin V-128 (AxV- 128/Tc) single photon emission computed tomography (SPECT)-computed tomography (CT) can detect perioperative lung injury. The investigators will study patients undergoing major surgery, specifically Whipple procedures (pancreatico-duodenectomies) and compare AxV-128/Tc SPECT-CT scans before and after surgery in Chronic Obstructive Pulmonary Disease (COPD) and non-COPD patients.

Detailed Description

Lung injury is commonly not detected unless structural damage has occurred. SPECT-CT scanning using a specific tracer that lights up when it detects apoptosis (programmed cell death) has been used to detect even minor lung injury for example by smoke inhalation in animals and may be more sensitive to detect a less severe injury. The present study aims to study SPECT-CT scan using a tracer for apoptosis, 99mTc Annexin V-128 (AxV- 128/Tc), to detect lung injury after major surgery. Prolonged ventilation during surgery can cause minor lung injury but is usually not clinically detected. The investigators are planning to study 40 patients (20 patients with pre-existing lung disease-COPD and 20 patients with normal preoperative lung function) who are undergoing Whipple operations or other major surgery. The investigators will obtain SPECT-CT scans before and then 2-3 days after surgery and compare the uptake of a radioactive tracer with plasma markers of lung injury (Soluble Receptors for Advanced Glycation End Products (sRAGE), Interleukin 6 (IL-6), Clara-cell 16 and lung surfactant protein D (SP-D) among others). The investigators will ask the subjects to undergo spirometry testing, blood draws and urine collection. In addition, a SPECT-CT scan that lasts approximately 1 hour will be performed prior to surgery and 2-3 days post-operatively (while still hospitalized).

The total effective dose from the combined SPECT and CT scans is 6.2 millisievert (mSv). This effective dose is below what a patient receives during a standard 2 dose rest and stress cardiac nuclear imaging study and well within the range of current clinical nuclear imaging tests. The exact long term risk for development of cancer from diagnostic radiological procedures is currently under debate but all imaging procedures in this study are aimed to keep total radiation burden As Low As Reasonably Achievable (ALARA).

Study Timeline

• Study First Submitted: 2016-11-28
• Study First Submitted QC: 2016-11-29
• Study First Posted: 2016-12-01
• Study Start: 2018-06-11
• Primary Completion: 2020-02-05
• Study Completion: 2020-02-05
• Status Verified: 2021-08
• Results First Submitted: 2021-08-17
• Results First Submitted QC: 2021-08-17
• Last Update Submitted: 2021-08-17
• Results First Posted: 2021-09-14
• Last Update Posted: 2021-09-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

• Patients with moderate COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II: forced expiratory volume 1 (FEV1)/forced vital capacity (FVC) <0.70 and FEV1 50-79% normal) undergoing Whipple procedures or other major surgeries
• Patients with normal lung function undergoing Whipple procedures or other major abdominal surgeries

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Exclusion Criteria

• Age < 18 years

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Preoperative COPD	SPECT-CT imaging	Patients with moderate COPD undergoing Whipple procedures or other major surgeries will receive an injection of AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
Normal preoperative lung function	AxV-128/Tc	Patients with normal lung function undergoing Whipple procedures or other major surgeries will receive an injection of AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
Normal preoperative lung function	Whipple procedure	Patients with normal lung function undergoing Whipple procedures or other major surgeries will receive an injection of AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
Normal preoperative lung function	Major surgery	Patients with normal lung function undergoing Whipple procedures or other major surgeries will receive an injection of AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
Preoperative COPD	AxV-128/Tc	Patients with moderate COPD undergoing Whipple procedures or other major surgeries will receive an injection of AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
Preoperative COPD	Major surgery	Patients with moderate COPD undergoing Whipple procedures or other major surgeries will receive an injection of AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
Normal preoperative lung function	SPECT-CT imaging	Patients with normal lung function undergoing Whipple procedures or other major surgeries will receive an injection of AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
Preoperative COPD	Whipple procedure	Patients with moderate COPD undergoing Whipple procedures or other major surgeries will receive an injection of AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).

Primary Outcome Measures

Name	Time	Method
Correlation of AxV-128/Tc Uptake and White Blood Cell (WBC) Count	Up to 1 week from initial scan	To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD
Correlation of AxV-128/Tc Uptake and Fibrinogen	Up to 1 week from initial scan	To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD
Correlation of AxV-128/Tc Uptake and C-Reactive Protein (CRP)	Up to 1 week from initial scan	To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD

Secondary Outcome Measures

Name	Time	Method
AxV-128/Tc Uptake	Up to 1 week from initial scan	To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD
Correlation of AxV-128/Tc Uptake and SP-D	Up to 1 week from initial scan	To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD
Correlation of AxV-128/Tc Uptake and IL-6	Up to 1 week from initial scan	To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD
Correlation of AxV-128/Tc Uptake and Clara-cell 16	Up to 1 week from initial scan	To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD
Correlation of AxV-128/Tc Uptake and RAGE	Up to 1 week from initial scan	To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD

Trial Locations

Locations (1)

Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States