PneumoniaPhase 1NCT02598713
Validation of Aspiration Markers in Intubated Patients
A Phase 1 study testing Aspiration Marker in people with Pneumonia and Aspiration, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The goal of this interventional study is to test Quinine as marker of aspiration (endotracheal tube [ETT] cuff leakage) in mechanically ventilated, critically ill patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pneumonia, Aspiration
- What is being tested?
- Aspiration Marker
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2015to 30 Jun 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Admission to Surgical ICUs (MGH Ellison 4 or Blake 12)
- Patients expected to be intubated for at least 48 hours or longer from the time of enrollment.
Who cannot join
- High PEEP requirement at enrollment (PEEP higher than 8 cmH2O)
- Diagnosis of ARDS (any severity)
- Status asthmatics
- Current or past participation in another interventional trial conflicting with the present study
- Pregnant women
- Prisoner status
- Patients who had partial or total gastrectomy.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachussets General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Validation of Markers for Aspiration for Endotracheal Tube Cuff Leak
The goal of this interventional study is to test Quinine as marker of aspiration (endotracheal tube [ETT] cuff leakage) in mechanically ventilated, critically ill patients.
Read the detailed description
At present there is no standard method for the evaluation of in vivo cuff leak and aspiration. Most of the tested techniques have major pitfalls that render their routine application infeasible. Lacking a practical and reliable marker, any possible intervention aimed at improving cuff seal and ETT performance in order to reduce VAP occurrence is going to be hindered by the inability to truly evaluate its efficacy. Radio-labeled markers are expensive, expose the patient to considerable radiological risk, and require transport to a radiological department, which would expose critically ill patients to additional risk. Dyes have the potential to give useful information about the presence of a cuff leak, but due to persistent staining of secretions, they do not allow continuous monitoring of aspiration. Amylase detection could be a good marker of aspiration, but its ability to detect aspiration is poor even when compared to pepsin. Pepsin and bile acids have the potential to detect some of the aspirations and cuff leaks that happen daily in mechanically ventilated patients, but due to their gastrointestinal nature, they do not offer any kind of information about aspiration of contaminated oropharyngeal secretions. With this research protocol, the investigators would like to validate the use of Quinine suspended in sterile water as marker for determining cuff leakage and aspiration events in an ICU population. Quinine is compound commonly used in food manufacturing. His pharmacokinetic and -dynamic has extensively been studied. The chemical structure of this molecule allows the detection up to pico-molar concentration by spectrophotometry.
The investigators will challenge the oropharyngeal cavity with a known concentration of Quinine suspended in sterile water. The investigators hypothesized that the detection by spectrophotometry of the same substance in the tracheal secretions will prove aspiration.
The investigators specific aims are:
- To quantify the measurements of Quinine in the tracheal sample and compare with the measurements of Quinine in the oral sample.
- To assess association between the amount of oropharyngeal aspiration and the development of upper and lower respiratory complications (i.e. ventilator associated pneumonia [VAP], tracheobronchitis, ventilator-associated events, acute respiratory distress syndrome [ARDS], etc.).
- To determine patient's risk factors associated with oropharyngeal aspiration. The introduction of this new, safe and inexpensive markers for evaluating ETT cuff performance and for detecting aspiration will improve the design of future studies aimed at VAP prevention.
- Conditions
- Pneumonia, Aspiration
- Being tested
- Aspiration Marker
- Medical subject headings
- Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aspiration MarkerDrug
Instillation of Quinine suspended in sterile water in the retropharyngeal space of intubated ICU admitted patients for two consecutive days.
| Study group | Role | What they receive |
|---|---|---|
| Aspiration Markers | Experimental | Aspiration marker solution will be composed as following: Quinine 83 mg/L suspended in sterile water. After enrollment patients will be challenged with 5 mL of the study solution nebulized in the retropharyngeal space twice a day for two consecutive days. Receives: Drug: Aspiration Marker |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oropharyngeal aspiration: change in concentration of quinine in tracheal samples.
The investigators will collect samples of oral and tracheal secretions below the endotracheal tube's cuff. Samples will be centrifuged and the supernatant tested by spectrophotometry. The presence of the study compound in the tracheal samples will be a sign of cuff leak and aspiration. The ratio between the concentration of the study molecules in the oral sample and in the collected samples will be used to give an estimate of leakage.
Measured: After the beginning of the study, samples will be collected at hours: 0,1 and 24, 25
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2015 (estimated)
- Study startDec 2015
- Primary completion30 Jun 2024 (estimated)
- Study completion30 Jun 2024 (estimated)
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for PneumoniaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lorenzo Berra, MD, Massachusetts General Hospital
- Investigators
- Lorenzo Berra, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02598713
- Sponsor's protocol ID
- Aspiration Markers
- Status last verified
- Nov 2025
- First submitted
- 2 Nov 2015
- Last updated
- 2 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
Publications
Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med. 2002 Apr 1;165(7):867-903. doi: 10.1164/ajrccm.165.7.2105078.
PubMed 11934711Berra L, Panigada M, De Marchi L, Greco G, Z -Xi Y, Baccarelli A, Pohlmann J, Costello KF, Appleton J, Mahar R, Lewandowski R, Ravitz L, Kolobow T. New approaches for the prevention of airway infection in ventilated patients. Lessons learned from laboratory animal studies at the National Institutes of Health. Minerva Anestesiol. 2003 May;69(5):342-7.
PubMed 12768164Feldman C, Kassel M, Cantrell J, Kaka S, Morar R, Goolam Mahomed A, Philips JI. The presence and sequence of endotracheal tube colonization in patients undergoing mechanical ventilation. Eur Respir J. 1999 Mar;13(3):546-51. doi: 10.1183/09031936.99.13354699.
PubMed 10232424Li Bassi G, Luque N, Marti JD, Aguilera Xiol E, Di Pasquale M, Giunta V, Comaru T, Rigol M, Terraneo S, De Rosa F, Rinaudo M, Crisafulli E, Peralta Lepe RC, Agusti C, Lucena C, Ferrer M, Fernandez L, Torres A. Endotracheal tubes for critically ill patients: an in vivo analysis of associated tracheal injury, mucociliary clearance, and sealing efficacy. Chest. 2015 May;147(5):1327-1335. doi: 10.1378/chest.14-1438.
PubMed 25500677Metheny NA, Clouse RE, Chang YH, Stewart BJ, Oliver DA, Kollef MH. Tracheobronchial aspiration of gastric contents in critically ill tube-fed patients: frequency, outcomes, and risk factors. Crit Care Med. 2006 Apr;34(4):1007-15. doi: 10.1097/01.CCM.0000206106.65220.59.
PubMed 16484901Mietto C, Pinciroli R, Patel N, Berra L. Ventilator associated pneumonia: evolving definitions and preventive strategies. Respir Care. 2013 Jun;58(6):990-1007. doi: 10.4187/respcare.02380.
PubMed 23709196
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Validation of Markers for Aspiration for Endotracheal Tube Cuff Leak
- ClinicalTrials.gov ID
- NCT02598713
- Acronym / sponsor ID
- Aspiration Markers
- Conditions
- Pneumonia, Aspiration
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Dec 2015
- Primary completion
- 30 Jun 2024 (estimated)
- Study completion
- 30 Jun 2024 (estimated)
- First posted
- 6 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this interventional study is to test Quinine as marker of aspiration (endotracheal tube [ETT] cuff leakage) in mechanically ventilated, critically ill patients.
Detailed description
At present there is no standard method for the evaluation of in vivo cuff leak and aspiration. Most of the tested techniques have major pitfalls that render their routine application infeasible. Lacking a practical and reliable marker, any possible intervention aimed at improving cuff seal and ETT performance in order to reduce VAP occurrence is going to be hindered by the inability to truly evaluate its efficacy. Radio-labeled markers are expensive, expose the patient to considerable radiological risk, and require transport to a radiological department, which would expose critically ill patients to additional risk. Dyes have the potential to give useful information about the presence of a cuff leak, but due to persistent staining of secretions, they do not allow continuous monitoring of aspiration. Amylase detection could be a good marker of aspiration, but its ability to detect aspiration is poor even when compared to pepsin. Pepsin and bile acids have the potential to detect some of the aspirations and cuff leaks that happen daily in mechanically ventilated patients, but due to their gastrointestinal nature, they do not offer any kind of information about aspiration of contaminated oropharyngeal secretions. With this research protocol, the investigators would like to validate the use of Quinine suspended in sterile water as marker for determining cuff leakage and aspiration events in an ICU population. Quinine is compound commonly used in food manufacturing. His pharmacokinetic and -dynamic has extensively been studied. The chemical structure of this molecule allows the detection up to pico-molar concentration by spectrophotometry.
The investigators will challenge the oropharyngeal cavity with a known concentration of Quinine suspended in sterile water. The investigators hypothesized that the detection by spectrophotometry of the same substance in the tracheal secretions will prove aspiration.
The investigators specific aims are:
- To quantify the measurements of Quinine in the tracheal sample and compare with the measurements of Quinine in the oral sample.
- To assess association between the amount of oropharyngeal aspiration and the development of upper and lower respiratory complications (i.e. ventilator associated pneumonia [VAP], tracheobronchitis, ventilator-associated events, acute respiratory distress syndrome [ARDS], etc.).
- To determine patient's risk factors associated with oropharyngeal aspiration. The introduction of this new, safe and inexpensive markers for evaluating ETT cuff performance and for detecting aspiration will improve the design of future studies aimed at VAP prevention.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Aspiration Markers | Experimental | Drug: Aspiration MarkerAspiration marker solution will be composed as following: Quinine 83 mg/L suspended in sterile water. After enrollment patients will be challenged with 5 mL of the study solution nebulized in the retropharyngeal space twice a day for two consecutive days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age ≥ 18 years
- Admission to Surgical ICUs (MGH Ellison 4 or Blake 12)
- Patients expected to be intubated for at least 48 hours or longer from the time of enrollment.
Key exclusion criteria (7 listed)
- High PEEP requirement at enrollment (PEEP higher than 8 cmH2O)
- Diagnosis of ARDS (any severity)
- Status asthmatics
- Current or past participation in another interventional trial conflicting with the present study
- Pregnant women
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aspiration MarkerInstillation of Quinine suspended in sterile water in the retropharyngeal space of intubated ICU admitted patients for two consecutive days. | Drug | Aspiration Markers |
Primary outcome
Oropharyngeal aspiration: change in concentration of quinine in tracheal samples.
Time frame: After the beginning of the study, samples will be collected at hours: 0,1 and 24, 25
The investigators will collect samples of oral and tracheal secretions below the endotracheal tube's cuff. Samples will be centrifuged and the supernatant tested by spectrophotometry. The presence of the study compound in the tracheal samples will be a sign of cuff leak and aspiration. The ratio between the concentration of the study molecules in the oral sample and in the collected samples will be used to give an estimate of leakage.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2025.
- Background: PubMed 11934711Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med. 2002 Apr 1;165(7):867-903. doi: 10.1164/ajrccm.165.7.2105078.
- Background: PubMed 12768164Berra L, Panigada M, De Marchi L, Greco G, Z -Xi Y, Baccarelli A, Pohlmann J, Costello KF, Appleton J, Mahar R, Lewandowski R, Ravitz L, Kolobow T. New approaches for the prevention of airway infection in ventilated patients. Lessons learned from laboratory animal studies at the National Institutes of Health. Minerva Anestesiol. 2003 May;69(5):342-7.
- Background: PubMed 10232424Feldman C, Kassel M, Cantrell J, Kaka S, Morar R, Goolam Mahomed A, Philips JI. The presence and sequence of endotracheal tube colonization in patients undergoing mechanical ventilation. Eur Respir J. 1999 Mar;13(3):546-51. doi: 10.1183/09031936.99.13354699.
- Background: PubMed 25500677Li Bassi G, Luque N, Marti JD, Aguilera Xiol E, Di Pasquale M, Giunta V, Comaru T, Rigol M, Terraneo S, De Rosa F, Rinaudo M, Crisafulli E, Peralta Lepe RC, Agusti C, Lucena C, Ferrer M, Fernandez L, Torres A. Endotracheal tubes for critically ill patients: an in vivo analysis of associated tracheal injury, mucociliary clearance, and sealing efficacy. Chest. 2015 May;147(5):1327-1335. doi: 10.1378/chest.14-1438.
- Background: PubMed 16484901Metheny NA, Clouse RE, Chang YH, Stewart BJ, Oliver DA, Kollef MH. Tracheobronchial aspiration of gastric contents in critically ill tube-fed patients: frequency, outcomes, and risk factors. Crit Care Med. 2006 Apr;34(4):1007-15. doi: 10.1097/01.CCM.0000206106.65220.59.
- Background: PubMed 23709196Mietto C, Pinciroli R, Patel N, Berra L. Ventilator associated pneumonia: evolving definitions and preventive strategies. Respir Care. 2013 Jun;58(6):990-1007. doi: 10.4187/respcare.02380.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lorenzo Berra, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Aspiration Marker in people with Pneumonia and Aspiration, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 2 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Oropharyngeal aspiration: change in concentration of quinine in tracheal samples. (time frame: After the beginning of the study, samples will be collected at hours: 0,1 and 24, 25). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02598713, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2025.