Personalized Pain Management for Spinal Fusion

(PPAP Spine Trial)

Recruiting at 3 trial locations

Overseen By Carly Riedmann, MPH

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Senthilkumar Sadhasivam

Must be taking: Opioids

Disqualifiers: Serious illness, Preoperative severe pain, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

300 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this collaborative CTSA application is to develop an innovative perioperative precision analgesia platform (PPAP) to improve analgesia and reduce serious immediate and long-term adverse outcomes of perioperative opioids in children undergoing painful surgery.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who are using opioids before surgery.

What data supports the effectiveness of the Personalized Perioperative Analgesia Platform (PPAP) treatment for pain management in spinal fusion surgery?

Research suggests that patient-controlled analgesia (PCA), a component of PPAP, is effective in managing postoperative pain by allowing patients to control their pain relief, which can lead to higher satisfaction and better pain management. Additionally, individualizing pain management strategies, as done in PPAP, is shown to improve outcomes by addressing each patient's unique pain perception and needs. ^{1 2 3 4 5}

Is personalized pain management for spinal fusion safe for humans?

Patient-controlled analgesia (PCA), a method used in personalized pain management, is generally safe for humans, though it can have side effects like nausea, vomiting, and respiratory issues. These side effects are often related to opioid use and can be managed by adjusting doses and monitoring patients closely. ^{2 6 7 8 9}

How is the Personalized Perioperative Analgesia Platform (PPAP) treatment different from other treatments for pain management after spinal fusion?

The Personalized Perioperative Analgesia Platform (PPAP) is unique because it likely offers a tailored approach to pain management, potentially combining different methods like patient-controlled analgesia (PCA) with personalized adjustments to better suit individual patient needs, unlike standard treatments that may not be as customizable. ^{2 8 9 10 11}

Research Team

Senthilkumar Sadhasivam, MD, MPH

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for children aged 10 to nearly 18, in good to moderate health (ASA status 1-3), who will need opioids during and after a specific back surgery called Posterior-Lateral Spinal Fusion. They can't join if they have serious illnesses, already suffer from severe pain before the operation, or use/misuse opioids beforehand.

Inclusion Criteria

I was prescribed opioids when I was discharged.

I am between 10 and 17 years old.

I am currently receiving opioids in a hospital.

Exclusion Criteria

I experience severe pain before surgery.

You have a severe medical condition.

You have been using or misusing opioids before your surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative

Preoperative CYP2D6 genotyping and collection of pharmacogenetic data

1 week

1 visit (in-person)

Surgery and Immediate Post-operative

Children undergo spine fusion surgery and immediate post-operative monitoring for opioid-adverse effects

4 days

Inpatient stay

Post-operative

Monitoring of genetic factors and personalized analgesia plan implementation

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of chronic persistent surgical pain and opioid dependence

Up to 1 year

Treatment Details

Interventions

• Personalized Perioperative Analgesia Platform (PPAP)
• Preoperative Genotyping

Trial Overview The study is developing a personalized pain management system for kids having spine fusion surgery. It involves preoperative genotyping—testing their genes—to tailor pain treatment and minimize opioid-related risks.

Participant Groups

Group I: Children undergoing Spine Fusion Surgery Experimental Treatment 1 Intervention

This arm will include approximately 300 children undergoing spine fusion surgery 1. Pharmacokinetic (PK): collection of 10-13 serial blood samples to determine serum levels of methadone/oxycodone and its metabolites 2. Pharmacogenetic (PG): Preoperative CYP2D6 genotyping (for preferential recruitment of CYP2D6 PMs and UMs). This will be collected in the pre-operative clinic via blood if there are clinical labs needed for standard of care. If no blood is needed in the pre-op clinic, the investigators will collect this via saliva. Postoperative Analgesia Dose and PK Sampling Schedule: Clinical care providers are blinded to CYP2D6/CYP2B6 when prescribing oxycodone/methadone; and genetic analysis of proposed targeted genes. Results of these samples will be used to determine personalized analgesia plan.

Who Is Running the Clinical Trial?

Senthilkumar Sadhasivam

Lead Sponsor

Trials

5

Recruited

3,200+

Senthil Sadhasivam

Lead Sponsor

Trials

7

Recruited

4,200+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

A patient-controlled analgesia (PCA) ratio of demands to deliveries ≥1.5 can predict higher morphine requirements and greater pain scores in the first 24 hours after scoliosis surgery, based on a study of 147 adolescents.

Patients with a PCA ratio ≥1.5 also experienced more opioid-related side effects and had longer hospital stays, indicating that this ratio could be a useful tool for identifying those at risk for severe postoperative pain and complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early postoperative patient-controlled analgesia ratio predicts 24-hour morphine consumption and pain in children undergoing scoliosis surgery. Matava, CT., Crawford, MW., Pehora, C., et al.[2014]

In a study of 93 children and adolescents aged 8 to 21 who underwent spinal fusion, patient-controlled analgesia (PCA) with morphine sulfate did not significantly reduce pain levels over the first four postoperative days, with many reporting moderate-to-severe pain.

Despite the use of PCA, patient satisfaction with pain relief was only rated as 'fair' to 'good', suggesting that effective pain management may require a combination of pharmacologic and nonpharmacologic therapies rather than relying solely on high-tech solutions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Children's use of PCA following spinal fusion. Kotzer, AM., Foster, R.[2019]

The cold pack test can effectively identify male patients who are likely to experience higher levels of postoperative pain after third molar surgery, with significant differences in pain scores observed between low and high pain tolerance groups.

Patients with low pain tolerance not only reported higher pain levels at various time points post-surgery but also consumed significantly more ibuprofen, indicating that assessing pain tolerance can help tailor analgesia strategies for better pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Predictive Value of Cold Pack Test for Pain After Third Molar Surgery. Kıraç Can, SB., Berkel, G., Can, S.[2023]

Effective management of acute pain in orthopedic and trauma patients requires individualized approaches, especially in postoperative settings where pain can change rapidly.

Patient-controlled analgesia (PCA) enhances patient satisfaction by allowing individuals to actively participate in their pain management, and combining different analgesic classes can improve efficacy while reducing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Acute pain therapy in orthopedics/trauma surgery]. Rehart, S., Henniger, M., Arndt, M.[2019]

Epidural administration of meperidine through a patient-controlled analgesia (PCA) system provided effective postoperative pain relief for patients undergoing high abdominal surgery, with no significant side effects reported.

Patients using epidural meperidine required less additional analgesia compared to those receiving subcutaneous meperidine, indicating higher satisfaction and better pain management with the epidural method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Continuous epidural perfusion with meperidine on demand for the treatment of postoperative pain]. Balust, J., Boada, J., Taurà, P., et al.[2013]

The PCoA Acute patient-controlled analgesic dispenser was found to be safe and effective, with no severe adverse events reported during the study involving 70 patients across three medical centers.

Patients using the PCoA Acute took their pain medication significantly faster and reported lower pain scores compared to those receiving traditional nurse-dispensed opioids, indicating improved compliance and satisfaction with the new system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Evaluation of a Novel Technology for Oral Patient-Controlled Analgesia, the PCoA&#174; Acute Device, for Hospitalized Patients with Postoperative Pain, in Pilot Feasibility Study. Wirz, S., Conrad, S., Shtrichman, R., et al.[2018]

Patient Controlled Analgesia (PCA) allows patients to manage their own pain relief by self-administering opioids, which leads to improved pain control and reduced overall opioid consumption, as patients can titrate their doses based on their individual needs.

While PCA is effective, it carries risks such as respiratory depression and potential user errors, highlighting the importance of proper programming and monitoring to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Patient-controlled analgesia]. Scherpereel, P.[2011]

Patient-controlled analgesia (PCA) is an effective method for managing acute pain in various situations, including postoperative recovery, labor, and chronic pain, allowing patients to control their own pain relief through an infusion pump.

While PCA is generally safe and effective, common side effects include nausea, vomiting, and respiratory depression, which can be influenced by human factors like pharmacy preparation and device programming.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Update on Patient-Controlled Analgesia for Acute Postoperative Pain. Motamed, C.[2022]

In a study involving 10 adolescents undergoing spinal fusion for idiopathic scoliosis, patient-controlled analgesia (PCA) provided significantly better pain control compared to conventional intramuscular analgesia, as measured on a 10-point pain scale (p < 0.02).

Both PCA and intramuscular analgesia resulted in similar levels of sedation and no side effects, suggesting that PCA is a safe and effective option for postoperative pain relief in adolescents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-controlled versus conventional analgesia for postsurgical pain relief in adolescents. Walson, PD., Graves, PS., Mortensen, ME., et al.[2019]

Patient-controlled epidural analgesia (PCEA) provided better pain relief on the first and second postoperative days compared to patient-controlled intravenous analgesia (PCIA) after spinal fusion surgery, as indicated by lower Visual Analog Scale (VAS) scores.

However, patients using PCEA experienced a higher incidence of side effects such as pruritus and paresthesia compared to those using PCIA, suggesting a trade-off between improved pain management and increased side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of patient-controlled epidural analgesia and patient-controlled intravenous analgesia after spinal fusion surgery: a meta-analysis of randomized controlled trials. Tian, P., Fu, X., Li, ZJ., et al.[2018]

In a study of 72 patients undergoing spinal fusion surgery, patient-controlled epidural analgesia (PCEA) significantly reduced pain levels compared to patient-controlled IV analgesia (PCIA) throughout the recovery period.

Patients using PCEA not only experienced lower pain levels but also achieved functional milestones, like turning in bed, faster and reported higher satisfaction with their pain management compared to those using PCIA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative analgesia after major spine surgery: patient-controlled epidural analgesia versus patient-controlled intravenous analgesia. Schenk, MR., Putzier, M., Kügler, B., et al.[2006]

References

1. United States pubmed.ncbi.nlm.nih.gov

Early postoperative patient-controlled analgesia ratio predicts 24-hour morphine consumption and pain in children undergoing scoliosis surgery. [2014]

2. United States pubmed.ncbi.nlm.nih.gov

Children's use of PCA following spinal fusion. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

The Predictive Value of Cold Pack Test for Pain After Third Molar Surgery. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

[Acute pain therapy in orthopedics/trauma surgery]. [2019]

5. Spain pubmed.ncbi.nlm.nih.gov

[Continuous epidural perfusion with meperidine on demand for the treatment of postoperative pain]. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Clinical Evaluation of a Novel Technology for Oral Patient-Controlled Analgesia, the PCoA&#174; Acute Device, for Hospitalized Patients with Postoperative Pain, in Pilot Feasibility Study. [2018]

7. France pubmed.ncbi.nlm.nih.gov

[Patient-controlled analgesia]. [2011]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Update on Patient-Controlled Analgesia for Acute Postoperative Pain. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Patient-controlled versus conventional analgesia for postsurgical pain relief in adolescents. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Comparison of patient-controlled epidural analgesia and patient-controlled intravenous analgesia after spinal fusion surgery: a meta-analysis of randomized controlled trials. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Postoperative analgesia after major spine surgery: patient-controlled epidural analgesia versus patient-controlled intravenous analgesia. [2006]