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Coronary Artery DiseaseEarly Phase 1PATHFINDERNCT04016740

The PATHFINDER Study: A Feasibility Trial

A Early Phase 1 study testing Ropivacaine, Ketamine and Remifentanil in people with Coronary Artery Disease and Delirium, run by Beth Israel Deaconess Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The main purpose of this study is to determine whether a rational strategy of EEG guided multimodal general anesthesia using target specific sedative and analgesics could result in enhanced recovery after anesthesia and surgery, decrease in postoperative delirium, and decrease in long term postoperative cognitive… Read more about this study

Who is it for?
Ages 60 years and older
Conditions the study is for
Coronary Artery Disease, Delirium
What is being tested?
Ropivacaine, Ketamine and Remifentanil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
1 siteUnited States
Study dates
20 Aug 2019to 7 Jul 2020
Phase
Early 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 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ 60 years
  • Undergoing any of the following types of surgery with cardiopulmonary bypass limited to coronary artery bypass surgery (CABG), CABG+valve surgeries and isolated valve surgeries.

Who cannot join

  • Preoperative left ventricular ejection fraction (LVEF) <30%
  • Emergent surgery
  • Non-English speaking
  • Cognitive impairment as defined by total MoCA score < 10
  • Currently enrolled in another interventional study that could impact the primary outcome, as determined by the PI
  • Significant visual impairment
Show all 10Show fewer
  • Chronic opioid use for chronic pain conditions with tolerance (total dose of an opioid at or more than 30 mg morphine equivalent for more than one month within the past year)
  • Hypersensitivity to any of the study medications
  • Known history of alcohol (> 2 drinks per day) or drug abuse Active (in the past year) history of alcohol abuse (≥5 drinks/day for men or ≥4 drinks/day for women) as determined by reviewing medical record and history given by the patient
  • Liver dysfunction (liver enzymes > 4 times the baseline, all patients will have a baseline liver function test evaluation), history and examination suggestive of jaundice.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: Perioperative Multimodal General Anesthesia Focusing on Specific CNS Targets in Patients Undergoing Cardiac Surgeries

The main purpose of this study is to determine whether a rational strategy of EEG guided multimodal general anesthesia using target specific sedative and analgesics could result in enhanced recovery after anesthesia and surgery, decrease in postoperative delirium, and decrease in long term postoperative cognitive dysfunction up to 6 months following cardiac surgery.

Read the detailed description

The main purpose of this study is to determine whether a rational strategy of EEG guided multimodal general anesthesia using target specific sedative and analgesics could result in enhanced recovery after anesthesia and surgery, decrease in postoperative delirium, and decrease in long term postoperative cognitive dysfunction up to 6 months following cardiac surgery.

Specific Aim 1: The feasibility of implementing multimodal general anesthesia strategy in the Operating Rooms (OR) Specific Aim 2: The feasibility of implementing EEG guided sedation until extubation in the Intensive Care Unit (ICU) Specific Aim 3: The enhancement of recovery after surgery (shorter ventilation time, ICU stay, hospital length of stay) Specific Aim 4: To estimate the effect size of decrease in postoperative day (POD) and postoperative cognitive dysfunction (POCD) to power future large randomized trials

Keywords
Cardiopulmonary Bypass, Cardiac Surgery, analgesics
Medical subject headings
Coronary Artery Disease, Delirium

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RopivacaineDrug

    Intraoperative bilateral PIFB block with 20 mL of 0.25% Ropivicaine on either side of the sternum after anesthetic induction but before surgical incision

  • KetamineDrug

    Intraoperative infusion

  • RemifentanilDrug

    Intraoperative infusion

  • DexmedetomidineDrug

    Intraoperative infusion

  • RocuroniumDrug

    Intraoperative intermittent bolus

  • PropofolDrug

    Intraoperative infusion

  • SevofluraneDrug

    Intraoperative inhaled as needed

  • DexmedetomidineDrug

    Post-operative infusion

  • PropofolDrug

    Post-operative infusion

  • EEG monitoringDevice

    Perioperative monitoring

Study groups in NCT04016740
Study groupRoleWhat they receive
Multimodal General AnesthesiaExperimentalIntraoperative The anesthesiologists involved in this study will be trained to infer differences in anti-nociception, unconsciousness movement and changes during other perioperative events by monitoring EEG. They will also be trained in titrating hypnotic and nociceptic medications based on changes in EEG. 1. Routine anesthetic induction 2. Bilateral Pectoro-interfascial block (PIFB) with 20 mL of 0.25% ropivacaine on either side of the sternum after anesthetic induction but before surgical incision 3. Ketamine (0.06 to 0.12 mg.kg/hr) 4. Remifentanil (0.05-0.2 mcg/kg/min) 5. Dexmedetomidine (0.2-1.0 mcg/kg/hr) 6. Rocuronium intermittent bolus (TOF) 7. Propofol infusion ± Sevoflurane titrated based on EEG monitoring Postoperative 1. Standard pain management protocol 2. Dexmedetomidine infusion 0.2-1.4 mcg/kg/hr (EEG guided) 3. Infusion continued till extubation 4. Propofol infusion may be added/used for sedation based on the treating physician's discretion
Receives: Drug: Ropivacaine; Drug: Ketamine; Drug: Remifentanil; Drug: Dexmedetomidine; Drug: Rocuronium; Drug: Propofol; Drug: Sevoflurane; Device: EEG monitoring
Standard Practice with EEG monitoringOtherThe initial 2 patients will receive standard anesthesia practice and perioperative EEG monitoring will be recorded to learn the patterns associated with our standard practice.
Receives: Device: EEG monitoring

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Delirium

    Incidence of delirium will be analyzed in patients treated with the multi-modal approach. Delirium will be defined as an acute change in pre-operative baseline condition with additional features of inattention and either disorganized thinking and altered loss of consciousness, as defined by the Confusion Assessment Method (CAM)Assessment Method (CAM) algorithm postoperatively until discharge.

    Measured: Participants will be followed for the duration of the hospital stay, an average of 5 days

Secondary outcomes (8)

  1. Time to extubation

    Time to extubation will be noted from ICU data

    Measured: Time of ICU admission until time of extubation in ICU, an average of 6 hours

  2. Montreal Cognitive Assessment (MoCA)

    MoCA scores (total possible score is 30 points; a score of 26 or above is considered normal) at discharge will be reported in order to assess the occurrence of postoperative cognitive decline. Study staff trained in administering the assessments will collect the data.

    Measured: On the day of discharge, an average of 6 days

  3. Pain scores

    Patient reported pain scores on a scale from 0-10 (0 no pain,10 extreme pain), until discharge for the index admission.

    Measured: At 4-8 hourly intervals every day until discharge, an average of 6 days

  4. Total opioid and supplemental analgesic consumption

    The total opioid dosage and supplemental analgesic dosage received in the first 48 hours postoperatively will be abstracted from the medical record.

    Measured: 48 hours, post-operative

  5. ICU

    Total duration of stay in ICU for the index admission

    Measured: Time of ICU admission until time of discharge to hospital floor; through the hospital stay, an average of 5 days

  6. ICU/hospital length of stay

    Their stay in the hospital for the index admission

    Measured: Time of stay in the hospital until discharge to floor or rehab, an average of 5 days

  7. In-hospital complications

    stroke, myocardial infarction (MI), acute kidney injury, pneumonia, reintubation, congestive heart failure, sepsis, reopening of sternum and all-cause mortality

    Measured: 7 days post-op on an average

  8. Follow up incidence of delirium

    The follow up incidence of delirium will be analyzed at 1 month and 6 months after discharge. Delirium will be defined as an acute change in pre-operative baseline condition with additional features of inattention and either disorganized thinking and altered loss of consciousness, as defined by the MoCA/t-MoCA.

    Measured: Patients will be assessed for delirium at 1 month and 6 months following the date of surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jul 2019
  2. Study start20 Aug 2019
  3. Primary completion19 Feb 2020
  4. Study completion7 Jul 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Sequential
Model description
2 roll-in patients followed by 20 patients in the interventional model.
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04016740
Sponsor's protocol ID
2019P000407
Acronym
PATHFINDER
Status last verified
Jan 2021
First submitted
9 Jul 2019
Last updated
28 Jan 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Brown EN, Lydic R, Schiff ND. General anesthesia, sleep, and coma. N Engl J Med. 2010 Dec 30;363(27):2638-50. doi: 10.1056/NEJMra0808281. No abstract available.

    PubMed 21190458

  • Brown EN, Pavone KJ, Naranjo M. Multimodal General Anesthesia: Theory and Practice. Anesth Analg. 2018 Nov;127(5):1246-1258. doi: 10.1213/ANE.0000000000003668.

    PubMed 30252709

  • McNicol E, Horowicz-Mehler N, Fisk RA, Bennett K, Gialeli-Goudas M, Chew PW, Lau J, Carr D; Americal Pain Society. Management of opioid side effects in cancer-related and chronic noncancer pain: a systematic review. J Pain. 2003 Jun;4(5):231-56. doi: 10.1016/s1526-5900(03)00556-x.

    PubMed 14622694

  • Volkow ND, Collins FS. The Role of Science in the Opioid Crisis. N Engl J Med. 2017 Nov 2;377(18):1798. doi: 10.1056/NEJMc1711494. No abstract available.

    PubMed 29117474

  • Mulier J. Opioid free general anesthesia: A paradigm shift? Rev Esp Anestesiol Reanim. 2017 Oct;64(8):427-430. doi: 10.1016/j.redar.2017.03.004. Epub 2017 Apr 18. No abstract available. English, Spanish.

    PubMed 28431750

  • MacKenzie KK, Britt-Spells AM, Sands LP, Leung JM. Processed Electroencephalogram Monitoring and Postoperative Delirium: A Systematic Review and Meta-analysis. Anesthesiology. 2018 Sep;129(3):417-427. doi: 10.1097/ALN.0000000000002323.

    PubMed 29912008

  • Depth of anaesthesia monitors - Bispectral Index (BIS), E-Entropy and Narcotrend-Compact M | Guidance and guidelines | NICE [Internet]. [cited 2018 Dec 24];Available from: https://www.nice.org.uk/guidance/dg6

  • Wildes TS, Mickle AM, Ben Abdallah A, Maybrier HR, Oberhaus J, Budelier TP, Kronzer A, McKinnon SL, Park D, Torres BA, Graetz TJ, Emmert DA, Palanca BJ, Goswami S, Jordan K, Lin N, Fritz BA, Stevens TW, Jacobsohn E, Schmitt EM, Inouye SK, Stark S, Lenze EJ, Avidan MS; ENGAGES Research Group. Effect of Electroencephalography-Guided Anesthetic Administration on Postoperative Delirium Among Older Adults Undergoing Major Surgery: The ENGAGES Randomized Clinical Trial. JAMA. 2019 Feb 5;321(5):473-483. doi: 10.1001/jama.2018.22005.

    PubMed 30721296

  • Wilson PT, Spitzer RL. Major changes in psychiatric nomenclature. Reconciling existing psychiatric medical records with the new American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. Hosp Community Psychiatry. 1968 Jun;19(6):169-74. No abstract available.

    PubMed 5661463

  • Sauer AM, Slooter AJ, Veldhuijzen DS, van Eijk MM, Devlin JW, van Dijk D. Intraoperative dexamethasone and delirium after cardiac surgery: a randomized clinical trial. Anesth Analg. 2014 Nov;119(5):1046-52. doi: 10.1213/ANE.0000000000000248.

    PubMed 24810262

  • Rudolph JL, Jones RN, Levkoff SE, Rockett C, Inouye SK, Sellke FW, Khuri SF, Lipsitz LA, Ramlawi B, Levitsky S, Marcantonio ER. Derivation and validation of a preoperative prediction rule for delirium after cardiac surgery. Circulation. 2009 Jan 20;119(2):229-36. doi: 10.1161/CIRCULATIONAHA.108.795260. Epub 2008 Dec 31.

    PubMed 19118253

  • Burkhart CS, Dell-Kuster S, Gamberini M, Moeckli A, Grapow M, Filipovic M, Seeberger MD, Monsch AU, Strebel SP, Steiner LA. Modifiable and nonmodifiable risk factors for postoperative delirium after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2010 Aug;24(4):555-9. doi: 10.1053/j.jvca.2010.01.003. Epub 2010 Mar 15.

    PubMed 20227891

  • Arora RC, Djaiani G, Rudolph JL. Detection, Prevention, and Management of Delirium in the Critically Ill Cardiac Patient and Patients Who Undergo Cardiac Procedures. Can J Cardiol. 2017 Jan;33(1):80-87. doi: 10.1016/j.cjca.2016.08.020. Epub 2016 Oct 5.

    PubMed 28024558

  • Delirium: prevention, diagnosis and management | Guidance and guidelines | NICE [Internet]. [cited 2018 Dec 20];Available from: https://www.nice.org.uk/guidance/cg103

  • Pesonen A, Suojaranta-Ylinen R, Hammaren E, Kontinen VK, Raivio P, Tarkkila P, Rosenberg PH. Pregabalin has an opioid-sparing effect in elderly patients after cardiac surgery: a randomized placebo-controlled trial. Br J Anaesth. 2011 Jun;106(6):873-81. doi: 10.1093/bja/aer083. Epub 2011 Apr 6.

    PubMed 21474474

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Ropivacaine, Ketamine and Remifentanil in people with Coronary Artery Disease and Delirium, run by Beth Israel Deaconess Medical Center 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 2 inclusion and 10 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: finished, as of the sponsor's last update on 28 Jan 2021. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence of Delirium (time frame: Participants will be followed for the duration of the hospital stay, an average of 5 days). 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 NCT04016740, which also lists 24 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 28 Jan 2021.

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The PATHFINDER Study: A Feasibility Trial | AzTrials