Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05525923 |
| Other study ID # |
STUDY22070047 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 1, 2023 |
| Est. completion date |
October 31, 2024 |
Study information
| Verified date |
May 2023 |
| Source |
OpalGenix, Inc |
| Contact |
Amy Monroe, MPH, MBA |
| Phone |
412-623-6382 |
| Email |
monroeal[@]upmc.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The proposed research is an important extension of an ongoing perioperative personalized
analgesia and intravenous opioid pharmacogenetic research. This research focuses on two of
the most commonly used oral opioid analgesics, oxycodone, and methadone, in adults following
thoracic surgery. Major inpatient thoracic surgeries (TS) for lung disease are common and
extremely painful surgeries and are associated with sever post-surgical pain, high incidence
of chronic post-surgical pain (CPSP), excess opioid use, costly immediate postoperative
opioid adverse events (AEs), and long hospital stays. This study is aiming to develop
proactive risk prediction algorithms for precision surgical pain relief in adult TS patients
through comparison of actual clinical outcomes with standard of care to predicted outcomes
based on personalized risk assessments.
Description:
Risks associated with post-TS pain and opioids. Opioids are still widely used to manage acute
surgical pain and remain a core component of enhanced recovery after surgery protocols (ERAS)
for painful TS. With current approaches that incorporate ERAS protocols, half of TS patients
still suffer from uncontrolled severe surgical pain and significant adverse opioid effects
due to opioids' narrow therapeutic indices and unpredictable inter-individual variations in
pain perception and opioid responses. Risks associated with perioperative opioid use include
immediate risks (life-threatening respiratory depression (RD), excessive sedation,
postoperative nausea and vomiting (PONV), urinary retention, constipation, ileus and itching)
frequently delay recovery, require additional treatment or monitoring, increase cost of care,
and prolong hospital stay. Long-term risks include CPSP, opioid dependence, OUD, and the
consequent personal, financial and societal burden of opioid epidemic. Post-TS CPSP: A 10%
increase in the percentage of time in severe pain on the first postoperative day was
associated with a 30% increase in the incidence of CPSP at 12 months (N=889),
post-thoracotomy pain and TS are associated with the highest risk for CPSP compared with all
other procedures. Effective and aggressive acute surgical pain management is critical to
lower risks of developing CPSP.
Opioids are still an important part of managing surgical pain following TS. Postoperative
pain following TS is often excruciating and challenging to treat as it provokes nociceptive,
neuropathic and spasmodic muscle pain. Current standardized ERAS multimodal analgesic
approaches include non-opioid analgesics to minimize opioids during and after surgery. While
ERAS protocols have reduced immediate perioperative opioid use, they follow a "one size fits
all" trial-and-error reactive standardized practice, and at risk patients continue to
experience uncontrolled pain, CPSP, costly opioid AEs and persistent opioid use.
High inter-individual variations in response to opioids can be explained by genetics, yet
translational barriers prevent widespread adoption of genotype-guided care: Our many studies
on genetic predictors of postoperative pain and opioid-related AEs, and published literature
from other researchers demonstrate that genetic and clinical factors are associated with
inter-individual variations in surgical pain and opioid AEs. Personalized care based on
validated and actionable polygenic and modifiable clinical risk factors (e.g., anxiety,
depression, catastrophizing, poorly controlled acute postoperative pain) can transform and
enhance post-TS pain and opioid management. Thus, there is an urgent and unmet need for a
highly reliable preoperative tool to predict and prevent severe pain, CPSP and opioid-related
AEs.
Inadequate acute postoperative pain management predisposes patients to the development of
CPSP and contributes to opioid dependence (OD), opioid misuse, and loss of productivity in
society. Opioids are continued after discharge in 76.4% of patients, with a median discharge
prescription of 150 mg oral morphine equivalents. More than a third of thoracic surgical
patients develop CPSP at 3 months after surgery and poor postoperative pain control predicts
both incidence and severity of CPSP. Patients who develop CPSP have a high life-long risk of
opioid use and misuse contributing to addiction, and overdose deaths.
Poorly controlled surgical pain, excessive opioid use, and CPSP lead to postoperative
neurocognitive disorders including delirium, postoperative cognitive dysfunction (POCD), and
dementia. Delirium is detected during hospitalization and neurocognitive decline lasting
longer (>30 days) is described as POCD. Untreated pain and excessive perioperative opioids
increase the risk of delirium and POCD in elderly individuals. A population-level Health and
Retirement study of 10,065 patients >62 years old showed CPSP is common and was associated
with accelerated memory decline and increased probability of dementia.
Both poorly controlled pain and excess opioid use predispose elderly surgical patients to
postoperative delirium, POCD and dementia. New persistent opioid use is a significant public
health problem in elderly surgical patients.
The OpalGenix Solution: GPS-Analgesics. As a Global Positioning System (GPS) helps chart a
course in unknown/unfamiliar terrain, GPS-Analgesics TM (Genotype-guided Physician Support
for Analgesics Use) is designed to support physicians to proactively identify patients
genetically predisposed to high risks for severe surgical pain, CPSP and opioid AEs. In this
Phase I proposal, OpalGenix will build on our prior studies to develop and validate
GPS-Analgesics in TS patients. We have extensively and prospectively studied ~2000 patients
undergoing painful surgeries and demonstrated that the high individual variation observed in
responses to surgical pain and opioids can be explained by a combination of polygenetic and
clinical factors. Specifically, inter-individual surgical pain, and opioid variability were
partly and independently explained by specific polymorphisms of the genes ABCB123, OPRM143,
CYP2B6110, ABCC351,52, FAAH22, COMT53 and OCT151. However, these single-gene associations
independently explain only a small (5-15%) portion of inter-individual variability in pain-
and opioid responses. GPS-Analgesics is a novel combinatorial pharmacogenetic polygenetic
tool with high accuracy (>90%) integrating clinical risk factors to better explain the
cumulative effects (>90%) of both polygenetic (50-60%) and clinical (40-50%) risk factors on
surgical pain and analgesics responses. OpalGenix's novel prototype predictive software
algorithm based on patented polygenic risks already has >80% predictivity. At the end of this
Phase I, GPS-Analgesics will provide >90% high accuracy, evidence-based, personalized
surgical pain while avoiding opioid-related AEs.
