PainINVISIBLENCT07473115
Individualized Analgesia in the Intensive Care Unit With a New Pain Assessment Bundle and Protocolized Analgesia Adjustments
An observational study of Pain and Pain Management, run by University of Zurich at 1 site in Switzerland.
Trial summary
Both severe pain and opioid therapy are associated with negative effects. The experience of pain is common in the intensive care unit, but it is highly individual and difficult to assess, as patients are often unable to communicate. This especially applies to patients who are mechanically ventilated. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pain, Pain Management, Critical Illness
- How many people
- 400 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Apr 2026to 31 Mar 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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
Study population: Mechanically ventilated adult patients in the intensive care unit.
Who may be able to join
- Part A
- Admission to the intensive care unit
- Adults (≥18 years) of all sex and gender
- Mechanical ventilation Part B
- Admission to the intensive care unit
- Adults (≥18 years) of all sex and gender
Show all 11Show fewer
- mechanical ventilation
- Continuous opioid therapy
- Richmond Agitation Sedation Scale (RASS) ≤ -4
- Presumed duration of mechanical ventilation until the end of observations (until day 3)
- Established vascular access suitable for blood sampling independent of study inclusion (arterial line or central venous catheter)
Who cannot join
- Part A
- None Part B
- Previous enrolment into the current investigation
- Tracheostomy
- Chronic opioid use
- Regional anaesthesia
Show all 16Show fewer
- Implanted pacemaker device
- Allergy to silicone or ECG-electrodes
- Ophthalmologic disease (e.g. ocular trauma, glaucoma) or past eye surgery
- Fixed pupils
- Known or suspected neurologic disease (including hypoxic encephalopathy)
- Therapy with atropine or topical mydriatics in previous 24 hours or planned
- Therapy with systemic steroids in previous 24 hours or planned
- Therapy with neuromuscular blocking agents in previous 24 hours or planned
- Stomatitis
- Active oral or nasal bleeding
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site
University Hospital Zurich
Zurich, Canton of Zurich, 8091
Institute of Intensive Care Medicine, +41 44 255 23 76, intensivmedizin@usz.ch
About this study
Official title: Individualized Analgesia in the Intensive Care Unit With a New Pain Assessment Bundle and Protocolized Analgesia Adjustments (INVISIBLE) - an Observational Single-Centre Study in Critically Ill Patients
Both severe pain and opioid therapy are associated with negative effects. The experience of pain is common in the intensive care unit, but it is highly individual and difficult to assess, as patients are often unable to communicate. This especially applies to patients who are mechanically ventilated. Behavioral assessment tools can help to identify pain in this population, but do not register overdose of opioid therapy. The AlgiScan® delivers the Pupillary Pain Index (PPI), an objective assessment of nociception level, which has been shown to be useful in small studies with respect to reduction of opioid dose without leading to more pain.
New institutional protocols for the assessment of pain include the behavioral pain assessment tool Zurich Observational Pain Assessment (ZOPA) and the PPI. This project aims to evaluate the impact of the new institutional protocols on opioid administration and occurrence of pain compared to a historical cohort by analyzing routinely collected data during mechanical ventilation (Part A). In a second part (Part B), promising biomarkers for detection of pain, subjective ratings by nurses and physicians and an additional behavioral pain scale will be evaluated using an observational study design. After screening and enrolment (day 1/visit 1), characteristics of pain will be assessed on 4 occasions during 2 days (day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5). On visit 2 and 4, biomarkers (alpha-amylase, cortisol) will be sampled.
- Conditions
- Pain, Pain Management, Critical Illness
- Keywords
- Pain assessment, Pain management, Critical illness, mechanical ventilation, intensive care unit, Pupillary pain index
- Medical subject headings
- Pain, Agnosia, Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Prospective Cohort | Critically ill and mechanical ventilated patients after implementation of a new institutional protocol for pain assessment and analgesia adjustments | |
| Historic Cohort | Critically ill and mechanical ventilated patients before implementation of a new institutional protocol for pain assessment and analgesia adjustments |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oral morphine equivalent (OME) per day of mechanical ventilation.
OME is a standardized method to quantify and compare the potency of different opioid drugs by converting their doses into the equivalent amount of oral morphine. Doses are weighted based on the potency of the opioid and then summarized into a final value. Days of mechanical ventilation are weighted based on the hours of mechanical ventilation divided by 24 hours (relevant for days of intubation and extubation).
Measured: Part A: during mechanical ventilation (up to 28 days)
Secondary outcomes (25)
Sufentanil dose per day of mechanical ventilation
average dose [mcg/min]
Measured: Part A: during mechanical ventilation (up to 28 days)
Opioid dose adjustments - Number of adjustments
Number of dose adjustments [/hour] and direction
Measured: Part A: during mechanical ventilation (up to 28 days)
Opioid dose adjustments - Relative change during pain assessment
Relative change of dose 45min after vs. 15min before ZOPA/PPI
Measured: Part A: during mechanical ventilation (up to 28 days)
Zurich Observational Pain Assessment (ZOPA)
The Zurich Observational Pain Assessment (ZOPA) is a validated behavioural pain assessment tool routinely used in the intensive care unit. The ZOPA includes 13 items in 4 categories. Each item is rated on a binary scale (yes or no), resulting in a minimum of zero and a maximum of 13 points. One or more positive item (meaning the item is rated with "yes") is interpreted as probable existing pain.
Measured: Part A: during mechanical ventilation Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Number of rescue analgesics administered per day
Bolus administration of opioids
Measured: Part A: during mechanical ventilation (up to 28 days)
Occurrence of adverse effects of pain per day of mechanical ventilation
- Intravenous antihypertensive treatment [y/n]
- Atrial fibrillation [y/n]
- anti-infective treatment [y/n]
- Richmond Agitation Sedation Scale (RASS) > +1 [y/n]
Measured: Part A: during mechanical ventilation (up to 28 days)
Number of sedatives used per day of mechanical ventilation
Average number of sedatives used in the intensive care unit (e.g. Propofol, Clonidine, Dexmedetomidine, Ketamine, Sevoflurane and Midazolam)
Measured: Part A: during mechanical ventilation (up to 28 days)
Richmond Agitation Sedation Scale (RASS) < -3
Duration of Richmond Agitation Sedation Scale (RASS) < -3 per total ventilation days. The RASS is a validated 10-point scale with a range from -5 (unarousable) to +4 (combative), with 0 being "alert and calm".
Measured: Part A: during mechanical ventilation (up to 28 days)
Time to extubation
Time to extubation from stop of analgosedation [hours]
Measured: Part A: From time of stop of analgosedation (during mechanical ventilation, up to 28 days) until extubation (up to 7 days). Events such as death or referrals while being intubated will be censored.
Opioid prescription at ICU discharge
- Opioid prescription at ICU discharge [y/n] in patients discharged alive (as listed in the ICU discharge report)
Measured: Part A: at ICU discharge assessed up to 5 days
Opioid prescription at hospital discharge
- Opioid prescription at hospital discharge [y/n] in patients discharged alive (as listed in the hospital discharge report)
Measured: Part A: at hospital discharge assessed up to 10 days
Target nociception level
Target Pupillary Pain Index. The Pupillary Pain Index (PPI) is a scale with range from 1 to 9 indicating the pupillary response to a noxious stimulus. A lower value indicates a deeper nociception level (a more intense stimulus is necessary to trigger pupillary dilation). A higher value indicates a lighter nociception level (a less intense stimulus triggers pupillary dilation).
Measured: Part A: during mechanical ventilation (up to 28 days)
Opioid-free days in the ICU
Days free of opioid administration [%]
Measured: Part A: from ICU admission to ICU discharge (up to 100 days)
Pupillary Pain Index
Objective pain measurement of nociception level. The Pupillary Pain Index (PPI) is a scale with range from 1 to 9 indicating the pupillary response to a noxious stimulus. A lower value indicates a deeper nociception level (a more intense stimulus is necessary to trigger pupillary dilation). A higher value indicates a lighter nociception level (a less intense stimulus triggers pupillary dilation).
Measured: - Part A: During mechanical ventilation - Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Cortisol
blood and saliva levels [nmol/L]
Measured: Part B: day 2/visit 2, day 3/visit 4
Amylase
blood and saliva [U/L]
Measured: Part B: day 2/visit 2, day 3/visit 4
Critical Care Pain Observation Tool (CPOT)
Validated behavioural pain assessment tool used in other intensive care units. The CPOT evaluates 4 dimensions. A score of 2 or less is regarded as likely minimal to no pain. A score of more than 2 is regarded as unacceptable level of pain.
Measured: Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Subjective pain rating
Questionnaire based rating of pain [y/n] by physician and nurses
Measured: Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Subjective rating of nociception level
Questionnaire based rating of nociception level [light/moderate/deep] by physician and nurses:
- light: moderate stimulus triggers pain
- moderate: strong stimulus triggers pain
- deep: strong stimulus does not trigger pain
- Rated by physicians and ICU nurses
Measured: Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Trust in the Zurich Observational Pain Assessment (ZOPA)
Trust rated by ICU physicians and ICU nurses on a numeric scale with a range from 0 to 10. 0 indicates no trust in the ZOPA and 10 indicates maximal trust in the ZOPA.
Measured: Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Trust in the Pupillary Pain Index (PPI)
Trust rated by ICU physicians and ICU nurses on a numeric scale with a range from 0 to 10. 0 indicates no trust in the PPI and 10 indicates maximal trust in the PPI.
Measured: Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Pupil size before stimulation
Pupil size before stimulation PPI measurement [mm]
Measured: Part A: during mechanical ventilation (up to 28 days)
Percentage pupil's variation
Pupil variation [%] during PPI measurement
Measured: Part A: during mechanical ventilation (up to 28 days)
Maximal size variation
Maximal variation in pupil size [mm] during PPI measurment.
Measured: Part A: during mechanical ventilation (up to 28 days)
Neuron-specific Enolase (NSE) [mcg/L]
NSE [mcg/L] in patients after cardiac arrest at 24, 48 and 72 hours
Measured: Part A: From cardiac arrest until 72 hours after cardiac arrest
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2026
- Study start1 Apr 2026 (estimated)
- Primary completion31 Mar 2027 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PainStudies of the same condition, open and under way.
- More trials run by University of ZurichThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rolf Erlebach, MD, Principal investigator, University of Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07473115
- Sponsor's protocol ID
- INVISIBLE
- Acronym
- INVISIBLE
- Status last verified
- Mar 2026
- First submitted
- 22 Dec 2025
- Last updated
- 17 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Ethical restrictions
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Individualized Analgesia in the Intensive Care Unit With a New Pain Assessment Bundle and Protocolized Analgesia Adjustments (INVISIBLE) - an Observational Single-Centre Study in Critically Ill Patients
- ClinicalTrials.gov ID
- NCT07473115
- Acronym / sponsor ID
- INVISIBLE / INVISIBLE
- Conditions
- Pain, Pain Management, Critical Illness
- Keywords
- Pain assessment, Pain management, Critical illness, mechanical ventilation, intensive care unit, Pupillary pain index
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- 1 Apr 2026 (estimated)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 16 Mar 2026 (actual)
- 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.
Both severe pain and opioid therapy are associated with negative effects. The experience of pain is common in the intensive care unit, but it is highly individual and difficult to assess, as patients are often unable to communicate. This especially applies to patients who are mechanically ventilated. Behavioral assessment tools can help to identify pain in this population, but do not register overdose of opioid therapy. The AlgiScan® delivers the Pupillary Pain Index (PPI), an objective assessment of nociception level, which has been shown to be useful in small studies with respect to reduction of opioid dose without leading to more pain.
New institutional protocols for the assessment of pain include the behavioral pain assessment tool Zurich Observational Pain Assessment (ZOPA) and the PPI. This project aims to evaluate the impact of the new institutional protocols on opioid administration and occurrence of pain compared to a historical cohort by analyzing routinely collected data during mechanical ventilation (Part A). In a second part (Part B), promising biomarkers for detection of pain, subjective ratings by nurses and physicians and an additional behavioral pain scale will be evaluated using an observational study design. After screening and enrolment (day 1/visit 1), characteristics of pain will be assessed on 4 occasions during 2 days (day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5). On visit 2 and 4, biomarkers (alpha-amylase, cortisol) will be sampled.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prospective Cohort | – | –Critically ill and mechanical ventilated patients after implementation of a new institutional protocol for pain assessment and analgesia adjustments |
| Historic Cohort | – | –Critically ill and mechanical ventilated patients before implementation of a new institutional protocol for pain assessment and analgesia adjustments |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Mechanically ventilated adult patients in the intensive care unit.
Key inclusion criteria (11 listed)
- Part A
- Admission to the intensive care unit
- Adults (≥18 years) of all sex and gender
- Mechanical ventilation Part B
- Admission to the intensive care unit
Key exclusion criteria (16 listed)
- Part A
- None Part B
- Previous enrolment into the current investigation
- Tracheostomy
- Chronic opioid use
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Oral morphine equivalent (OME) per day of mechanical ventilation.
Time frame: Part A: during mechanical ventilation (up to 28 days)
OME is a standardized method to quantify and compare the potency of different opioid drugs by converting their doses into the equivalent amount of oral morphine. Doses are weighted based on the potency of the opioid and then summarized into a final value. Days of mechanical ventilation are weighted based on the hours of mechanical ventilation divided by 24 hours (relevant for days of intubation and extubation).
25 secondary outcomes
Sufentanil dose per day of mechanical ventilation
Time frame: Part A: during mechanical ventilation (up to 28 days)
Opioid dose adjustments - Number of adjustments
Time frame: Part A: during mechanical ventilation (up to 28 days)
Opioid dose adjustments - Relative change during pain assessment
Time frame: Part A: during mechanical ventilation (up to 28 days)
Zurich Observational Pain Assessment (ZOPA)
Time frame: Part A: during mechanical ventilation Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Number of rescue analgesics administered per day
Time frame: Part A: during mechanical ventilation (up to 28 days)
Occurrence of adverse effects of pain per day of mechanical ventilation
Time frame: Part A: during mechanical ventilation (up to 28 days)
Number of sedatives used per day of mechanical ventilation
Time frame: Part A: during mechanical ventilation (up to 28 days)
Richmond Agitation Sedation Scale (RASS) < -3
Time frame: Part A: during mechanical ventilation (up to 28 days)
Time to extubation
Time frame: Part A: From time of stop of analgosedation (during mechanical ventilation, up to 28 days) until extubation (up to 7 days). Events such as death or referrals while being intubated will be censored.
Opioid prescription at ICU discharge
Time frame: Part A: at ICU discharge assessed up to 5 days
Opioid prescription at hospital discharge
Time frame: Part A: at hospital discharge assessed up to 10 days
Target nociception level
Time frame: Part A: during mechanical ventilation (up to 28 days)
Opioid-free days in the ICU
Time frame: Part A: from ICU admission to ICU discharge (up to 100 days)
Pupillary Pain Index
Time frame: - Part A: During mechanical ventilation - Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Cortisol
Time frame: Part B: day 2/visit 2, day 3/visit 4
Amylase
Time frame: Part B: day 2/visit 2, day 3/visit 4
Critical Care Pain Observation Tool (CPOT)
Time frame: Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Subjective pain rating
Time frame: Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Subjective rating of nociception level
Time frame: Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Trust in the Zurich Observational Pain Assessment (ZOPA)
Time frame: Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Trust in the Pupillary Pain Index (PPI)
Time frame: Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Pupil size before stimulation
Time frame: Part A: during mechanical ventilation (up to 28 days)
Percentage pupil's variation
Time frame: Part A: during mechanical ventilation (up to 28 days)
Maximal size variation
Time frame: Part A: during mechanical ventilation (up to 28 days)
Neuron-specific Enolase (NSE) [mcg/L]
Time frame: Part A: From cardiac arrest until 72 hours after cardiac arrest
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2026.
- Individual participant dataSharing planned: No. Ethical restrictions
Related trials for Pain
Not yet recruiting
Effect of Stress Ball Use During Femoral Arterial Sheath Removal After Coronary Angiography
Femoral Arterial Sheath Removal, Stress Ball
Recruiting
Empowered Relief® for Cancer Survivors With Chronic Pain
Chronic Pain Due to Cancer, Pain Catastrophizing
RecruitingPhase 4
ESP Blocks for Posterior Spinal Fusion
Postoperative Pain
RecruitingObservational study
Pain Phenotypes in Individuals With Multiple Sclerosis
Multiple Sclerosis, Chronic Pain
Not yet recruiting
Effects of Hip Hinge Exercises on Pain, Range of Motion and Functional Disability in Non-specific Low Back Pain.
Low Back Pain
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.
Rolf Erlebach, MD principal investigator
University of Zurich
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pain and Pain Management, run by University of Zurich at 1 site in Switzerland.
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 11 inclusion and 16 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: opening soon, as of the sponsor's last update on 17 Mar 2026. 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 Switzerland. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sascha I David, Professor (+41 43 253 19 02, Sascha.David@usz.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Oral morphine equivalent (OME) per day of mechanical ventilation. (time frame: Part A: during mechanical ventilation (up to 28 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Mar 2026.