Precision Opioid Care After Cesarean Delivery (PRECISE-CD)
Study Details
Study Description
Brief Summary
The purpose of this research is to study serious clinical problems from both surgical pain and oxycodone and opioid use in women having a Cesarean Delivery to improve the safety and efficacy of surgical pain relief. This research will ultimately improve the safety and efficacy of surgical pain relief with opioids by preoperative risk predictions and personalized care with the right dose of the right analgesic for each patient.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
Detailed Description
The overall objective is to determine the impact of risk factors on oxycodone and other opioid's adverse postoperative outcomes and to personalize dosing in women having a Cesarean Delivery. For the purpose of this study, immediate adverse postoperative outcomes are characterized as Respiratory Depression (RD), Postoperative Nausea and Vomiting (PONV), and inadequate surgical pain relief. Long-term adverse postoperative outcomes are characterized as Chronic Persistent Surgical Pain (CPSP) and Opioid Dependence (OD).
The central hypothesis is that specific genetic factors in pain-opioid pathways significantly impact oxycodone and opioid dosing, analgesia, immediate adverse effects (RD and PONV), and long-term adverse outcomes (CPSP and OD) along with known non-genetic risk factors.
The aims of this project are to validate genetic variants and to develop a test for preoperative risk prediction in lactating mothers and breastfed babies following cesarean delivery (CD). There is an urgent and unmet critical need for reliable technology to improve safety and effectiveness of opioid use in special populations.
Aim 1. Validate and identify genetic risk factors associated with postoperative opioid adverse effects, PONV and RD in adult nursing mothers following CD.
Investigators hypothesize that with standardized and genotype-blinded perioperative care, specific variants will identify nursing mothers at risk for opioid-induced RD and PONV (primary outcome), OD and severe pain following CD. In addition, genetic variants will identify risk for opioid-induced sedation and adverse effects in breastfed infants. In addition to clinical outcomes, the investigators will collect post-CD cost of care including length of stay.
Aim 2. Develop a laboratory-developed test (LDT) at University of Pittsburgh Genome Center (UGC) for preoperative genetic risk prediction and decision support for surgical patients to prevent adverse opioid outcomes. Investigators will develop a minimum viable product (MVP) (CPT code: 81227), a refined multi-gene panel in UGC's CLIA certified laboratory with a robust combinatorial pharmacogenetic decision support to personalize surgical analgesia with precise opioid use in children and adults, and to prevent RD, PONV, CPSP and OD.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| MATERNAL cohort Nursing mothers who underwent Cesarean Delivery and who are receiving oxycodone to treat post-operative pain |
Drug: Oxycodone
exposure to opioids after Cesarean Section
Other Names:
|
| NEONATE-INFANT cohort Neonate" encompasses a newborn from the age of birth until <28 days of life. "Infant" refers to the period of 28 days of life until 1 year of life. |
Drug: Oxycodone
exposure to opioids after Cesarean Section
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Opioid-Induced Adverse Effects-Number of maternal participants with RD [From time of surgery to time of discharge up to 30 days post-surgery]
Respiratory depression (RD) is defined as respiratory rate <8 breaths per minute or SpO2. <94% along with a respiratory rate of <10 per minute requiring supplemental oxygen to maintain SpO2 >94% in the absence of upper airway obstruction.
- Opioid-Induced Adverse Effects-Number of maternal participants with PONV [From time of surgery to time of discharge up to 30 days post-surgery]
Postoperative Nausea and Vomiting (PONV) Intensity Scale. Minimum score: 0, Maximum score: 600. Clinically important PONV is defined as a total score >50 at any time throughout the study period.
- Opioid-Induced Adverse Effects-Number of maternal participants with sedation [From time of surgery to time of discharge up to 30 days post-surgery]
Ramsey Agitation Sedation Scale (RASS) Score from -5 (unarousable) to +4 (combative)
Secondary Outcome Measures
- Neonatal Sedation [From time of delivery to 1 week post delivery]
Defined as any sleeping > 4 hours in hospital or first week of life
- Neonatal Respiratory Depression [From time of delivery to time of discharge up to 30 days post-delivery]
Defined as respiratory rate 8 or less during hospitalization
- Total inpatient Opioid Use [From time of surgery to time of discharge up to 30 days post-surgery]
measured in Morphine Equivalence
- Length of prescribed opioids (in days) [From day of surgery to 12 months post-surgery]
Number of days patient taking opioids post-surgery
- Maternal Post-operative Pain Scores [From time of delivery to 12 months post-surgery]
Numerical Rating Scale (NRS). The pain scale is from 0 to 10, 0 being "no pain" and 10 being "the worst pain imaginable"
- Hospital Length of Stay-Maternal [From time of surgery to discharge or up to 30 days post surgery]
Time spent admitted to the hospital
- Hospital Length of Stay-Neonate [From time of delivery to 30 days post delivery]
time spent admitted to the hospital
- Presence of Chronic Persistent Surgical Pain (CPSP) [2, 3, 6, and 12 months after surgery]
CPSP is a binary measurement - "yes" if subject is experiencing pain post-surgery, and "no" if they are not experiencing pain. Pain lasting for at least 3-6 months post-surgery, significantly affecting the health-related quality of life.
- Neonate/Infant opioid withdrawal [From time of delivery to time of discharge up to 30 days post-delivery]
Sophia Observation withdrawal Symptoms-scale (SOWSS). Minimum score: 0 Maximum score:15. Score of >4 is positive for withdrawal symptoms.
- Neonatal Limpness [every twelve hours after delivery until discharge up until 30 days]
NRS Limpness scale 0-10, where 0 is none and 10 is the worst imaginable limpness
- Presence of Neonatal Hypothermia [From time of delivery to time of discharge up to 30 days post-delivery]
Clinical assessment by a licensed physician to determine if hypothermia is present
Other Outcome Measures
- CYP2D6 genotyping will be utilized to characterize CYP2D6 Poor Metabolizers (PMs) and Ultrarapid Metabolizers (UMS)-neonatal [Obtained during controlled delivery]
A blood sample will be collected to assess polymorphisms of genotypes, epigenetics and gene expression affecting opioid effectiveness, metabolism and transport. CYP2D6 genotyping
- CYP2D6 genotyping will be utilized to characterize CYP2D6 Poor Metabolizers (PMs) and Ultrarapid Metabolizers (UMS)-maternal [Obtained during controlled delivery]
A blood sample will be collected to assess polymorphisms of genotypes, epigenetics and gene expression affecting opioid effectiveness, metabolism and transport. CYP2D6 genotyping
- Opioid dependence (OD) [5-7 days after surgery and 3 to 12 months after surgery]
Clinical Opiate Withdrawal Scale (COWS). Minimum score: 0, Maximum score: 31. The higher the score, the more severe the withdrawal syndrome.
- Opioid Misuse Prediction [Before scheduled surgery and 1 week and 3 months post-op]
Opioid Risk Tool- score of 3 or less indicates low risk for future opioid use, 4-7 indicates moderate risk, score of 8 or higher indicates high risk
- Quality of Life after surgery [1, 3, 6, 12 months post-op]
WHO Quality of Life Scale (0-100). Minimum score: 4, Maximum score: 20. Raw scores are converted to percentage values which is on a typical 0-100 scale.
- Quality of Breastfeeding [From time of surgery to time of discharge up to 30 days post-surgery]
LATCH Assessment Tool. The LATCH tool assigns a numerical score of 0, 1, or 2 to five key components of breastfeeding for a possible score of 10 points. Minimum score: 0, Maximum score: 10. Clinically a mom needs to have a score of 8 or higher to be discharged.
- Screener and Opioid Assessment for Patients with Pain- Revised (SOAPP®-R) [1 week post-op and 1, 3, 6, 12 months post-op]
Minimum score: 0, Maximum score: 96. A score of 18 or higher is considered positive.
- Functional Recovery after surgery [1 week and 3, 6, 12 months post-op]
Functional Disability Inventory (FDI). Minimum score: 0, Maximum score: 60. Higher scores indicate greater general functional limitations or increasing difficulty with the tasks and activities.
- Pain Catastrophizing Scale [From day of surgery to 12 months post-op]
13 items scored from 0-4 with high score of 52, higher score indicates increased pain Catastrophizing
Eligibility Criteria
Criteria
Inclusion Criteria:
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Pregnant Adult women (>18 y) and their infants
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All races
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ASA physical status 2 to 3
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Cesarean delivery at UPMC Magee
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Planned breast feeding mothers and their infants
Exclusion Criteria:
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Serious illnesses or condition of either mother or infant precluding ability to participate in study procedures
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Multiple gestation pregnancies
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Preoperative severe pain and opioid use/misuse
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Allergy to oxycodone
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Women with opioid use disorder
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Any known condition that anticipates neonatal observation in NICU immediately after birth
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General anesthesia anticipated or converted intraoperatively
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Expected non-viable current gestation or serious neonatal health comorbidities anticipated prior to delivery
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Severe neurological disorder: any known untreated or uncontrolled seizure disorder, pre-eclampsia with severe features, pre-eclampsia requiring magnesium, elevated ICP other than benign intracranial hypertension condition, or conditions at the discretion of PI
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Liver disease: any known abnormal live function tests, or conditions at the discretion of PI
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Renal diseases: any chronic or acute renal insufficiency, or pre-eclampsia diagnosis with abnormal renal function i.e.: severe features, or conditions at the discretion of PI.
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Contraindications to neuraxial anesthesia, neuraxial morphine, acetaminophen, or NSAIDs which are standard parts of post-cesarean multimodal analgesia
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Magee Women's Hospital of UPMC | Pittsburgh | Pennsylvania | United States | 15213 |
Sponsors and Collaborators
- Grace Lim, MD, MS
Investigators
- Principal Investigator: Grace Lim, MD MSc, University of Pittsburgh
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- STUDY21070164