NIVATS Versus IGAVATS: a Pilot Trial Addressing Biopsy Quality in Undetermined Interstitial Lung Diseases

Study Overview
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Brief Summary
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The main objective of this study is to compare two independent groups of patients requiring lung biopsy for undetermined interstitial lung disease (ILD) in terms of diagnostic confidence as determined by histologists.

Detailed Description
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The primary objective of this study is to compare two independent groups of patients requiring lung biopsy for undetermined interstitial lung disease (ILD) in terms of diagnostic confidence as determined by histologists. The experimental arm will be operated under a neoteric non-intubated video assisted thoracic surgery (NIVATS) technique and the comparator arm under a usual intubated general anaesthesia video-assisted thoracic surgery (IGAVATS) technique. Secondarily, the two groups will also be compared in terms of: (i) further variables associated with histology, biopsy quality and size; (ii) surgical performance, (iii) patient trajectories and lung function; (iv) quality of life, and (v) harms.

Official Title
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Video-assisted Thoracic Surgery for Lung Biopsy Using Non-intubated (NIVATS) Versus Intubated General Anaesthesia (IGAVATS): a Randomized, Controlled, Pilot Trial Addressing Biopsy Quality in Undetermined Interstitial Lung Diseases

Conditions
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Lung Diseases, Interstitial

Intervention / Treatment
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* Procedure: Non-intubated video-assisted thoracic surgery (NIVATS) for lung biopsy
* Procedure: Intubated general anaesthesia video-assisted thoracic surgery (IGAVATS) for lung biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with purported interstitial lung disease Patient requiring a surgical lung biopsy to reinforce diagnosis according to current recommendations and validated by a multidisciplinary assessment Minimum age: 18 years Exclusion Criteria: Contra-indication for surgery Uncontrolled oesophageal gastric reflux despite optimal treatment Thoracic deformation (For example, pectus excavatum/carinatum or major scoliosis) Risk of pleural adhesion (For example, patient who has already undergone thoracic surgery) History of abnormal bleeding Predictable risk of difficult intubation Body mass index (BMI) > 30 Severe cardiovascular comorbidity (For example, instable ischemic cardiomyopathy) Unable to comply with all trial procedures/visits (For example, language barriers, upcoming move of household to another region, unwillingness to schedule the required followup visits.) Protected populations according to the French Public Health Code Articles L1121-5,6,8 (For example, pregnant, parturient or lactating women, prisoners, adults under guardianship or otherwise unable to consent.) Potential interference from another study (The patient is participating in another interventional study, or has done so in the past month, or is affected by an exclusion period stipulated by a previous study.) Non-beneficiary of the French single-payer national medical insurance system Lack of signed informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: In this prospective, parallel group, randomized (1:1), controlled, pilot trial, screening will take place during routine multidisciplinary assessment (MDA) meetings. The study is then presented to eligible patients during their next pre-surgical visits; if the patients are interested in participating, informed consent procedures are completed (again during routine visits) and the patients are randomized to two arms. In the experimental arm, patients will undergo NIVATS for lung biopsy, and in the standard arm, patients will undergo traditional IGAVATS for lung biopsy. Histology is then performed as usual, before entering a centralized pathway for a second analysis by an expert external to the study, and a second routine MDA convened (both blinded to study arms). Patients are followed-up for 12 months.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NIVATS<br>Lung biopsy is performed using non-intubated video-assisted thoracic surgery (NIVATS). | Procedure: Non-intubated video-assisted thoracic surgery (NIVATS) for lung biopsy<br>* An epidural anaesthesia associated with mild sedation requiring no ventilation is used.<br>|
| Active Comparator: IGAVATS<br>Lung biopsy is performed using Intubated general anaesthesia video-assisted thoracic surgery (IGAVATS). | Procedure: Intubated general anaesthesia video-assisted thoracic surgery (IGAVATS) for lung biopsy<br>* Uses a traditional deep anaesthesia and one-lung ventilation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The level of diagnostic confidence based on centralized histology only | The level of diagnostic confidence for a given diagnosis is established according to a quantitative scale ranging from '0' (absolute rule-out) to '10' (diagnostic certainty). A visual guide for scale use is provided with scores <1 corresponding to alternate diagnosis, scores >=1 and <4 corresponding to indeterminate, scores >=4 and <7 corresponding to probable, and scores >=7 corresponding to highly probable categories. | Day 1 to day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The level of diagnostic confidence based on routine histology only | The level of diagnostic confidence for a given diagnosis is established according to a quantitative scale ranging from '0' (absolute rule-out) to '10' (diagnostic certainty). A visual guide for scale use is provided with scores <1 corresponding to alternate diagnosis, scores >=1 and <4 corresponding to indeterminate, scores >=4 and <7 corresponding to probable, and scores >=7 corresponding to highly probable categories. | Day 1 to day 15 | 
| The level of diagnostic confidence achieved at multidisciplinary assessment (MDA)-2 | The level of diagnostic confidence for a given diagnosis is established according to a quantitative scale ranging from '0' (absolute rule-out) to '10' (diagnostic certainty). A visual guide for scale use is provided with scores <1 corresponding to alternate diagnosis, scores >=1 and <4 corresponding to indeterminate, scores >=4 and <7 corresponding to probable, and scores >=7 corresponding to highly probable categories. | Day 7 to day 28 | 
| Change in the level of diagnostic confidence for the most favoured diagnosis between multidisciplinary assessment (MDA)-1 and multidisciplinary assessment (MDA)-2 | The level of diagnostic confidence for a given diagnosis is established according to a quantitative scale ranging from '0' (absolute rule-out) to '10' (diagnostic certainty). A visual guide for scale use is provided with scores <1 corresponding to alternate diagnosis, scores >=1 and <4 corresponding to indeterminate, scores >=4 and <7 corresponding to probable, and scores >=7 corresponding to highly probable categories. | Day 7 to day 28 | 
| Classification according to ATS/ERS at MDA-1 | Classification according to the American Thoracic Society / European Respiratory society: Alternative diagnosis / Indeterminate / Probable / Highly probable | Day -28 to day -3 | 
| Classification according to ATS/ERS at MDA-2 | Classification according to the American Thoracic Society / European Respiratory society: Alternative diagnosis / Indeterminate / Probable / Highly probable | Day 7 to day 28 | 
| Inter-histologist concordance for ATS/ERS categories | Inter-histologist concordance for ATS/ERS categories | Day 1 to 15 | 
| Longest length (mm) of biopsy specimens | Longest length (mm) of biopsy specimens | Day 1 to 15 | 
| Volume (cc) of biopsy specimens | Volume (cc) of biopsy specimens | Day 1 to 15 | 
| Weight (g) of biopsy specimens | Weight (g) of biopsy specimens | Day 1 to 15 | 
| Numerical scale for biopsy quality | The histologist ranks biopsy quality from worst imaginable (0) to excellent (10). | Day 1 to 15 | 
| Preparation time (minutes) | Minutes lapsed between entering the surgical ward and entering the operating room (OR) | Day 0 | 
| OR time (minutes) | Minutes lapsed between entering and exiting the OR | Day 0 | 
| Recovery room (RR) time (minutes) | Minutes lapsed between exiting the OR and exiting the surgical ward. | Day 0 | 
| Post-RR time (hours) | Hours lapsed between exit from surgical ward, and discharge from hospital | Day 1 to 15 | 
| First drink time (minutes) | Minutes lapsed between application of last bandage on surgical wounds to first drink | Day 0 | 
| Post-operative fasting time (hours) | Hours lapsed between application of last bandage on surgical wounds to first meal | Day 0 | 
| Time with chest tube in place (hours) | Hours lapsed between application of last bandage on surgical wounds to removal of chest tube | Day 0 | 
| Visual analogue scale score for post-operative pain | The patient will be asked to evaluate his/her level of post-operative pain using a numeric rating scale (0-10) the morning after surgery where 0 represents no pain, and 10 represents the worse possible pain. | Day 1, morning after surgery | 
| Patient satisfaction (satisfied vs unsatisfied) | The patient will be asked to evaluate his/her satisfaction (satisfied vs unsatisfied) | Hospital discharge (expected maximum of 15 days) | 
| Time to dischargeability | Dischargeability is defined as meeting the following criteria: (i) satisfactory pain control via oral analgesia; (ii) ability to mobilize and return to usual autonomy; (iii) absence of clinical, laboratory and radiological complications; (iv) stable respiratory state compatible pre-surgical state and home discharge; (v) vital signs are normal for the patient; (vi) chest tube removal >12 hours. | Days 1 to 15 | 
| Length of initial hospitalization stay (hours) | Length of initial hospitalization stay (hours) | Expected maximum of 15 days | 
| Cumulative days of hospitalization | Cumulative days of hospitalization | 12 months | 
| Cumulative days of exacerbation | Cumulative days of exacerbation | 12 months | 
| Days alive, not exacerbating and not in hospital | Days alive, not exacerbating and not in hospital | 12 months | 
| Forced vital capacity (litres) | Forced vital capacity (litres) | Day -28 to Day -1 | 
| Forced vital capacity (litres) | Forced vital capacity (litres) | 12 months | 
| Forced vital capacity (% theoretical value) | Forced vital capacity (% theoretical value) | Day -28 to Day -1 | 
| Forced vital capacity (% theoretical value) | Forced vital capacity (% theoretical value) | 12 months | 
| Euroqol 5 dimensions 5 levels questionnaire: mobility dimension score | In its original version, this self-administered questionnaire consists of two pages: the first contains the EQ-5D descriptive system and the second a visual analogue scale. The descriptive system has five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each described by five levels of intensity (no problems, slight problems, moderate problems, severe problems and extreme problems or complete inability). The respondent must indicate one intensity level for each dimension. | Day -28 to Day -1 | 
| Euroqol 5 dimensions 5 levels questionnaire: mobility dimension score | In its original version, this self-administered questionnaire consists of two pages: the first contains the EQ-5D descriptive system and the second a visual analogue scale. The descriptive system has five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each described by five levels of intensity (no problems, slight problems, moderate problems, severe problems and extreme problems or complete inability). The respondent must indicate one intensity level for each dimension. | 12 months | 
| Euroqol 5 dimensions 5 levels questionnaire: self-care dimension score | In its original version, this self-administered questionnaire consists of two pages: the first contains the EQ-5D descriptive system and the second a visual analogue scale. The descriptive system has five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each described by five levels of intensity (no problems, slight problems, moderate problems, severe problems and extreme problems or complete inability). The respondent must indicate one intensity level for each dimension. | Day -28 to Day -1 | 
| Euroqol 5 dimensions 5 levels questionnaire: self-care dimension score | In its original version, this self-administered questionnaire consists of two pages: the first contains the EQ-5D descriptive system and the second a visual analogue scale. The descriptive system has five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each described by five levels of intensity (no problems, slight problems, moderate problems, severe problems and extreme problems or complete inability). The respondent must indicate one intensity level for each dimension. | 12 months | 
| Euroqol 5 dimensions 5 levels questionnaire: usual activities dimension score | In its original version, this self-administered questionnaire consists of two pages: the first contains the EQ-5D descriptive system and the second a visual analogue scale. The descriptive system has five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each described by five levels of intensity (no problems, slight problems, moderate problems, severe problems and extreme problems or complete inability). The respondent must indicate one intensity level for each dimension. | Day -28 to Day -1 | 
| Euroqol 5 dimensions 5 levels questionnaire: usual activities dimension score | In its original version, this self-administered questionnaire consists of two pages: the first contains the EQ-5D descriptive system and the second a visual analogue scale. The descriptive system has five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each described by five levels of intensity (no problems, slight problems, moderate problems, severe problems and extreme problems or complete inability). The respondent must indicate one intensity level for each dimension. | 12 months | 
| Euroqol 5 dimensions 5 levels questionnaire: pain/discomfort dimension score | In its original version, this self-administered questionnaire consists of two pages: the first contains the EQ-5D descriptive system and the second a visual analogue scale. The descriptive system has five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each described by five levels of intensity (no problems, slight problems, moderate problems, severe problems and extreme problems or complete inability). The respondent must indicate one intensity level for each dimension. | Day -28 to Day -1 | 
| Euroqol 5 dimensions 5 levels questionnaire: pain/discomfort dimension score | In its original version, this self-administered questionnaire consists of two pages: the first contains the EQ-5D descriptive system and the second a visual analogue scale. The descriptive system has five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each described by five levels of intensity (no problems, slight problems, moderate problems, severe problems and extreme problems or complete inability). The respondent must indicate one intensity level for each dimension. | 12 months | 
| Euroqol 5 dimensions 5 levels questionnaire: anxiety/depression dimension score | In its original version, this self-administered questionnaire consists of two pages: the first contains the EQ-5D descriptive system and the second a visual analogue scale. The descriptive system has five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each described by five levels of intensity (no problems, slight problems, moderate problems, severe problems and extreme problems or complete inability). The respondent must indicate one intensity level for each dimension. | Day -28 to Day -1 | 
| Euroqol 5 dimensions 5 levels questionnaire: anxiety/depression dimension score | In its original version, this self-administered questionnaire consists of two pages: the first contains the EQ-5D descriptive system and the second a visual analogue scale. The descriptive system has five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each described by five levels of intensity (no problems, slight problems, moderate problems, severe problems and extreme problems or complete inability). The respondent must indicate one intensity level for each dimension. | 12 months | 
| Presence / absence of complications | Complications will be listed and classified (Minor: (1) Any complication without need for pharmacologic treatment or other intervention; (2) Any complication that requires pharmacologic treatment or minor intervention only; Major: (3) Any complication that requires surgical, radiologic, endoscopic intervention, or multitherapy; (3a) Intervention does not require general anesthesia; (3b) Intervention requires general anesthesia; (4) Any complication requiring intensive care unit management and life support; (4a) Single organ dysfunction; (4b) Multiorgan dysfunction; (5) Any complication leading to the death of the patient. | 12 months |