NIVATS Versus IGAVATS: a Pilot Trial Addressing Biopsy Quality in Undetermined Interstitial Lung Diseases (NIVATS-2)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Lung Diseases, Interstitial
• Intervention / Treatment: Procedure: Non-intubated video-assisted thoracic surgery (NIVATS) for lung biopsy; Procedure: Intubated general anaesthesia video-assisted thoracic surgery (IGAVATS) for lung biopsy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Timothée JOUITTEAU, Doctor; Phone Number: 003467335958; Email: t-jouitteau@chu-montpellier.fr

Study Locations

• France
  • Montpellier, France
    • Recruiting
    • Département d'Anesthésie et Réanimation Cardiothoracique - CHU Arnaud de Villeneuve
    • Contact: Timothée JOUITTEAU, Doctor; Phone Number: 003467335958; Email: t-jouitteau@chu-montpellier.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Collaborators: Grace Asso (Groupe francophone de Réhabilitation Améliorée après Chirurgie)

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2023
• Primary Completion (Estimated): November 24, 2025
• Study Completion (Estimated): November 24, 2025

Study Registration Dates

• First Submitted: January 18, 2023
• First Submitted That Met QC Criteria: January 31, 2023
• First Posted (Actual): February 10, 2023

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 18, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: RECHMPL 22_0042

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The general goal is to make the study data available to interested researchers as well as to provide proof of transparency for the study.

Data will be made available to persons who address a reasonable request to the study director.

Individual participant data (and an accompanying data dictionary) will be de-identified and potentially further cleaned or aggregated as the investigators deem necessary to protect participant anonymity.

The study protocol, participant Information materials, worksheet and data sharing plan will also be made available to the public.

IPD Sharing Time Frame

Datasets that underlie the results reported in the article (text, tables, figures, and appendices) can be requested after the publication process has been completed.

The study protocol will be published in an open-access, peer-reviewed journal. Other key documents will be made available on the Open Science Framework as they are finalized.

IPD Sharing Access Criteria

The conditions under which members of the public will be granted access to datasets are:

• The data will be used/examined in a not-for-profit manner;
• The data will not be used in an attempt to identify a participant or group of participants;
• The user does not work for a private insurance company;
• The data will not be used in support of any kind of private insurance policy or health penalties;
• The data will be used/examined for the advancement of science/teaching while respecting participant/patient privacy and rights;
• The user will state why they wish to access the data.
• If the data do not fulfil the requirements of the reference methodology (MR-00X) (ex: data about religion, etc.), the appropriate CNIL approval has to be obtained by the user.
• If the data will be used outside the European Union, standard contractual clauses have to be signed between Montpellier University Hospital and the user before sharing data.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No