An interventional study of NIVATS biopsy and TBLC biopsy in Interstitial Lung Diseases (ILD), sponsored by Rita Alexandra Afonso da Costa. Not yet recruiting at 1 site in Portugal. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-02.
Sponsored by Rita Alexandra Afonso da Costa · Not applicable, Interventional, and Diagnostic
Patients with suspected interstitial lung disease (ILD) may require a lung biopsy when clinical and imaging findings are inconclusive. This single-centre pilot study randomly assigns adults (1:1) to transbronchial lung cryobiopsy (TBLC) or to non-intubated video-assisted thoracoscopic surgical biopsy (NIVATS). Its main aims are to find out whether a larger trial is feasible (recruitment, acceptance of randomisation, completion of the assigned procedure, completeness of data) and to obtain preliminary estimates, with confidence intervals, of the diagnostic yield and the 30-day complication rate of each procedure. The study is not designed to demonstrate that one procedure is non-inferior or superior to the other; the results will be used to plan a multicentre confirmatory trial.
Despite concerns regarding morbidity and mortality, open surgical lung biopsy has traditionally been considered the gold standard. Although NIVATS and TBLC have emerged as minimally invasive alternatives, they have not yet been directly compared in a randomized clinical trial. Consequently, there is insufficient evidence to robustly compare the diagnostic yield and safety of these approaches, supporting the need for a pilot randomized trial before proceeding to a larger confirmatory study.
Participants will be randomized in a 1:1 ratio using a computer-generated randomization sequence with permuted blocks of variable size. Randomization will not be stratified. Allocation concealment will be ensured using sequentially numbered, opaque, sealed envelopes prepared by an independent investigator. Envelopes will be opened only after written informed consent has been obtained and the participant has been enrolled in the study. Owing to the nature of the interventions, blinding of patients, treating physicians, and pathologists will not be feasible.
The subjects of this study will be all patients with suspected ILD, who require histological diagnostic methods after clinical discussion in a multidisciplinary team (MDT) meeting. Patients who meet the inclusion criteria and have none of the exclusion criteria will be invited to participate in the study. After enrolment, participants will be randomized to NIVATS or TBLC; the assigned procedure should ideally be performed within one month of randomization. All outcomes will be assessed 30 days follow-up visit after the procedure.
No formal interim analysis of the primary endpoint is planned, as this is a pilot study. A separate administrative review after the first 15 participants (approximately 20% of the planned enrolment) will assess recruitment, procedural feasibility and data completeness; it will test no hypothesis and carry no statistical penalty. All deaths occurring during the study will be recorded and reviewed to assess their relationship to the study procedure. A death, or any unexpected serious adverse event, considered possibly or probably related to the procedure will trigger a temporary pause in enrolment and an independent safety review by a physician not involved in the study, and the Ethics Committee will be notified. The review will determine whether any modification of the study procedures or additional safety measures are required before enrolment resumes.
This study is designed as a single-center feasibility (pilot) trial. A confirmatory non-inferiority trial would require 142 participants per arm (284 in total), assuming a diagnostic yield of 90% in both arms, a one-sided type I error of 0.025, 80% power and a non-inferiority margin of 10 percentage points on the risk-difference scale (Farrington-Manning method). This exceeds the recruitment capacity of a single center within the planned 18-month period, during which approximately 37 participants per arm (74 in total) are attainable. The study is therefore not powered to confirm non-inferiority: with the attainable sample, the two-sided 95% confidence interval for the between-arm difference in diagnostic yield is expected to be approximately +/-14 percentage points, wider than the 10-point non-inferiority margin.
Primary analysis: The primary analysis will focus on estimating the difference in diagnostic yield (TBLC - NIVATS), with corresponding two-sided 95% confidence intervals. The study is not powered to establish non-inferiority conclusively. The 10-percentage-point margin that would be used in a confirmatory trial will serve as a reference for interpreting the confidence interval, rather than as the basis for a definitive confirmatory conclusion. Effect estimates and their confidence intervals will be reported in preference to p-values.
Secondary and safety analyses: Safety and secondary endpoints will be analysed descriptively, without formal hypothesis testing. The main safety endpoint is the procedure-related complication rate, defined as the proportion of participants experiencing at least one of the following events: procedure-related 30-day mortality, acute exacerbation of ILD, severe bleeding, pneumonia, empyema, pneumothorax requiring chest drain insertion (TBLC) or postoperative air leak (NIVATS). Binary endpoints (procedure-related complication rate) will be summarized as risk differences with 95% confidence intervals; length-of-stay and length-of-drainage, which are right-skewed and subject to a competing risk of death, will be summarized as medians with interquartile ranges. All secondary analyses are exploratory.
Estimates will be presented for both the ITT and PP populations; concordance between them will inform the choice of primary analysis population for the confirmatory trial. The PP population will include participants who undergo the procedure to which they were randomised and who have no major protocol deviations affecting assessment of the primary endpoint. Participants who crossover between treatment arms will remain in their randomised group for the ITT analysis and will be excluded from the corresponding PP analysis. In the ITT analysis, participants who do not undergo the allocated procedure will be classified as non-diagnostic. Results from any subsequent biopsy or repeat procedure will not contribute to the primary diagnostic-yield endpoint, and a non-diagnostic biopsy will be classified as an unsuccessful procedure.
680 studies on the registry are indexed under Lung Diseases, Interstitial; 246 are open to participants now.
This study's planned enrollment of 74 is above the median of 60 across 384 interventional studies indexed under Lung Diseases, Interstitial.
Browse Lung Diseases, Interstitial studies →This is the only study on the registry with Rita Alexandra Afonso da Costa as lead sponsor.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants randomised to lung biopsy by non-intubated VATS under sedation and regional anaesthesia
Procedure: NIVATS biopsy
Participants randomised to lung biopsy by TBLC under general anesthesia
Procedure: TBLC biopsy
NIVATS is a surgical technique performed under the patient's spontaneous respiration without tracheal intubation. Patients are brought to the operating room and placed in the contralateral lateral decubitus position. The anesthesiologist initiates deep sedation combined with local infiltration at the incision site and an intercostal block guided by thoracoscopy or an erector spinae block guided by ultrasound. The lung biopsy is always performed using automatic stapling devices, sampling peripheral areas in two different lobes-usually on the right side, including the middle lobe. All patients leave the operating room with a digital chest drain, which allows for quantification of the air leak.
TBLC is performed under general anesthesia with jet ventilation using a rigid bronchoscope (12 mm) as the main access route, through which a flexible bronchoscope is introduced. A 2.4 mm cryoprobe is used, along with real-time fluoroscopic guidance and a radial EBUS miniprobe to identify the target biopsy site. In selected cases, electromagnetic navigation can also be employed.Under fluoroscopic guidance, the cryoprobe is advanced to the selected segment until the pleural surface is reached, and then retracted 1 cm, with freezing times typically between 5 and 7 seconds. Following activation, the bronchoscope and cryoprobe are withdrawn together with the attached tissue sample.A total of 3 to 5 biopsies are generally performed per procedure, preferably from different segments within the same lobe, or different lobes from the same lung.
Histopathological diagnostic yield
Proportion of participants in each arm achieving a high confident histopathological diagnosis
Time frame: 30-day follow-up visit after the procedure
Procedure-related complications
Proportion of participants experiencing at least one complication: procedure-related 30-day mortality, acute exacerbation of ILD, severe bleeding, pneumonia, empyema, pneumothorax requiring chest drain insertion (TBLC) or postoperative air leak (NIVATS)
Time frame: 30-day follow-up visit after the procedure.
Multidisciplinary team diagnostic yield
Time frame: 30 days after intervention
Plan to share: Yes — De-identified individual participant data underlying the published results, the protocol and the SAP will be available from the PI on reasonable request, from 6 months to 5 years after publication, subject to a data-sharing agreement and GDPR.
Supporting information: Study protocol, Statistical analysis plan
Time frame: From 6 months to 5 years after publication
Access criteria: Requests for access to the IPD will be considered from qualified researchers who provide a reasonable research proposal describing the intended analyses and objectives. Requests must be submitted to the PI and will be reviewed on a case-by-case basis. The proposed analyses must be scientifically justified and compatible with the informed consent obtained from study participants and applicable data protection requirements
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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