PAIN - Postoperative Analgesia INvestigation (PAIN)

• ClinicalTrials.gov Identifier: NCT02111746
• Recruitment Status: Completed
• First Posted: April 11, 2014
• Results First Posted: October 16, 2018
• Last Update Posted: October 16, 2018
• Sponsor: The University of Texas Health Science Center, Houston
• Information provided by (Responsible Party): Kristofer Charlton-Ouw, The University of Texas Health Science Center, Houston

Study Description

Brief Summary:

The purpose of this study is to assess the efficacy of the intraoperative injection of prolonged acting (liposomal) bupivacaine in postoperative pain control after truncal surgical incisions.

Condition or disease	Intervention/treatment	Phase
Postoperative Pain	Drug: Exparel; Drug: Bupivacaine hydrochloride; Drug: Patient Controlled Analgesia (PCA)	Phase 4

Detailed Description:

Study Design:

This is a prospective, single-institution, parallel-group, single-blinded, randomized-controlled, two-arm, effectiveness study comparing bupivacaine liposomal injectable suspension (Exparel®) versus regular bupivacaine hydrochloride (HCl).

Procedure:

In patients aged 18 and over who require sternotomy, thoracotomy, mini-thoracotomy, or laparotomy incisions will be screened and consented for potential enrollment. Patients will be randomized following consenting to either Exparel® or regular bupivacaine hydrochloride group.

Course of Study:

The study will accrue patients over the course of 4 years.

Enrollment:

Enrollment will consist of all adult patients aged 18 and over undergoing surgical procedures requiring sternotomy, thoracotomy, mini-thoracotomy, or laparotomy incisions. Patients will be screened and consented preoperatively. If the patient is deemed eligible and consents to participate, randomization will occur and the patient will be considered enrolled.

Recruitment:

The target for enrollment will be 280 patients (the study target sample size per power analysis, but actual enrollment will be greater (330 patients) to account for exclusions for various reasons in order to achieve the target recruitment).

Risks:

There is a small increased risk to the patients by participating in the study in addition to a possible chance of breach in patient confidentiality as the study involves evaluation of an FDA-approved drug. As detailed in the informed consent, the subjects are at risk of developing adverse effects from Exparel®, described on the drug packet insert and from HCl Bupivacaine, also described on the drug packet insert. The investigators do not expect any additional physical risks other than an unintentional disclosure of sensitive patient health information.

Data Safety Monitoring:

As the Principal Investigator of this study, Dr. Charlton-Ouw from the Department of Cardiothoracic and Vascular Surgery at The University of Texas at Houston Medical School will conduct the data safety monitoring of this study. He will annually meet with all other co-investigators to review the patients enrolled in this study. As part of the data safety monitoring plan, all patients enrolled until that point in time would be unblinded in order to review the outcomes. Additionally, in view of the uncertainty attached to the treatment effects in this heterogeneous population, owing to limited currently available data, an independent Data Safety Monitoring Committee, will oversee the progress of the trial.

IND#:

The drugs that will be used are already approved by the FDA and do not have IND/IDE#

Proposed Funding Source:

The study is internally funded and is investigator-initiated.

Communication of Study Results:

The communication of study results will occur only between authorized individuals who are listed to take part in the study through our department. The individuals who will take part in the study will acknowledge and adhere to the importance of patient safety and the protection of their private information. The results of this study will be analyzed and published after the approval of the principal investigator, co-investigators, and biostatistician in a peer-reviewed scientific journal and/or presented at an international/national scientific conference or meeting regardless of outcome.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 350 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Prospective, blinded, controlled randomized clinical trial with 2-armed parallel-group sequential design
• Masking: Double (Participant, Investigator)
• Masking Description: Masking included all patients, who were blinded to the contents of the intraoperative injection, as well as partial blinding of the surgical team who were masked from the treatment allocation up until the time of injection following which the knowledge of drug was inevitable as Exparel® has a milky appearance as opposed to the colorless bupivacaine hydrochloride (standard) formulations.
• Primary Purpose: Treatment
• Official Title: A Prospective Randomized-controlled Study on Effectiveness of Extended-release Liposomal Bupivacaine in Postoperative Pain Control
• Actual Study Start Date: November 20, 2013
• Actual Primary Completion Date: May 3, 2017
• Actual Study Completion Date: June 30, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Exparel®; Patients in this group will receive will receive the study drug [bupivacaine liposomal injectable suspension (Exparel®)] and Patient Controlled Analgesia (PCA). Exparel® is an FDA-approved bupivacaine liposome injectable suspension produced by Pacira Pharmaceuticals.	Drug: Exparel; Participants will receive 266mg of liposomal bupivicaine (equivalent of one 1.3% 20ml vial of EXPAREL®) diluted in 60ml of preservative-free normal (0.9%) sterile saline for a total volume of 80mL. Drug will be administered at the end of the procedure just prior to wound closure.; Other Name: bupivacaine liposomal injectable suspension (Exparel®); Drug: Patient Controlled Analgesia (PCA); Patients will have access to the standard Patient Controlled Analgesia (PCA) offered at the Memorial Hermann Hospital - Texas Medical Center. The PCA drug will be Dilaudid (hydromorphone). Initial dosing will be per the standard hospital protocol of 0.2 mg demand dose, 10 minute lockout, 2 mg per hour max, 0.4 mg rescue dose. Adjustments to the PCA dosing will be made based on clinical needs. Patients will receive PCA until the third postoperative day
Active Comparator: Regular Bupivacaine; Patients in this group will receive will receive the standard regular bupivacaine hydrochloride (HCl) and PCA. Bupivacaine HCl is an FDA-approved injectable suspension. The standard non-liposomal bupivacaine will be from Hospira pharmaceuticals	Drug: Bupivacaine hydrochloride; Participants will receive 125mg of bupivacaine hydrochloride (equivalent of one 0.25% 50ml or five 0.25% 10ml vials ) diluted in 30ml of preservative-free normal (0.9%) sterile saline for a total volume of 80mL. Drug will be administered at the end of the procedure just prior to wound closure.; Other Name: Regular Bupivacaine; Drug: Patient Controlled Analgesia (PCA); Patients will have access to the standard Patient Controlled Analgesia (PCA) offered at the Memorial Hermann Hospital - Texas Medical Center. The PCA drug will be Dilaudid (hydromorphone). Initial dosing will be per the standard hospital protocol of 0.2 mg demand dose, 10 minute lockout, 2 mg per hour max, 0.4 mg rescue dose. Adjustments to the PCA dosing will be made based on clinical needs. Patients will receive PCA until the third postoperative day

Outcome Measures

Primary Outcome Measures :

1. Postoperative Pain as Assessed by a Numeric Pain Scale (NPS) [ Time Frame: postoperative day 1 ]
   The Numeric Pain Scale (NPS) ranges from 0 ("no pain") to 10 ("worst possible pain").
2. Postoperative Pain as Assessed by a Numeric Pain Scale (NPS) [ Time Frame: postoperative day 2 ]
   The Numeric Pain Scale (NPS) ranges from 0 ("no pain") to 10 ("worst possible pain").
3. Postoperative Pain as Assessed by a Numeric Pain Scale (NPS) [ Time Frame: postoperative day 3 ]
   The Numeric Pain Scale (NPS) ranges from 0 ("no pain") to 10 ("worst possible pain").
4. Postoperative Pain as Assessed by a Five-point Satisfaction Scale [ Time Frame: postoperative day 1 ]
   The 5-point satisfaction scale ranges from 1 (extremely dissatisfied) to 5 (extremely satisfied).
5. Postoperative Pain as Assessed by a Five-point Satisfaction Scale [ Time Frame: postoperative day 2 ]
   The 5-point satisfaction scale ranges from 1 (extremely dissatisfied) to 5 (extremely satisfied).
6. Postoperative Pain as Assessed by a Five-point Satisfaction Scale [ Time Frame: postoperative day 3 ]
   The 5-point satisfaction scale ranges from 1 (extremely dissatisfied) to 5 (extremely satisfied).
7. Postoperative Pain as Assessed by the Brief Pain Inventory (BPI) [ Time Frame: postoperative day 1 ]
   The Brief Pain Inventory (BPI) ranges from 0 ("no pain") to 10 ("worst pain you can imagine").
8. Postoperative Pain as Assessed by the Brief Pain Inventory (BPI) [ Time Frame: postoperative day 2 ]
   The Brief Pain Inventory (BPI) ranges from 0 ("no pain") to 10 ("worst pain you can imagine").
9. Postoperative Pain as Assessed by the Brief Pain Inventory (BPI) [ Time Frame: postoperative day 3 ]
   The Brief Pain Inventory (BPI) ranges from 0 ("no pain") to 10 ("worst pain you can imagine").

Secondary Outcome Measures :

1. Overall Opioid Use [ Time Frame: Over the first 72 hours after surgery ]
   The total amount in mg of opioid medication consumed through 12, 24, 36, 48, 60, and 72 hours after surgery will be assessed.
2. Mean Length of Hospital Stay [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 4 weeks ]
   Indirect outcome measure to assess the adequacy of postoperative pain control as an indicator of improvement in healing period, patient participation in physical therapy and faster patient mobilization, and overall health care cost
3. Change From Baseline in Quality of Life [ Time Frame: Will be assessed preoperatively, on the first post-op day (POD 1), on POD2, and POD 3 ]
   The impact of pain on patient's quality of life will be assessed through a brief pain inventory (BPI). In addition, the 5-point scale analgesia satisfaction survey will be used along with the BPI to assess patient satisfaction and quality of life.
4. Number of Participants Who Attain Physical Therapy Goal That Justifies Discharge From Inpatient Physical Therapy Within 72 Hours [ Time Frame: 72 hours after surgery ]
5. Hospital Cost for Patient Care During Hospitalization [ Time Frame: duration of hospital stay, an expected average of 4 weeks ]
   Hospital cost for patient care during hospitalization will be estimated from hospital charges and financial records.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 18 years-old or older, and
• Sternotomy, thoracotomy, laparotomy or mini-thoracotomy incision is planned
• There is reasonable expectation that the patient will be extubated within 24 hours after surgery

Exclusion Criteria:

• The patient has a known allergy to morphine or any opioid
• The patient has a known chronic pain disorder or takes daily opioid medication > 1 month prior to surgery
• There is anticipated difficulty communicating pain status due to language or other barriers at the investigator discretion
• High postoperative morbidity index based on preoperative assessment, such as, low likelihood of extubation within 24 hours, extensive thoracoabdominal aortic aneurysm (Extent 2 TAAA), preoperative renal insufficiency/failure, etc.

Contacts and Locations

Locations

United States, Texas

Department of Cardiothoracic and Vascular Surgery and Memorial Hermann Heart and Vascular Institute - Texas Medical Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

The University of Texas Health Science Center, Houston

Investigators

• Principal Investigator: Kristofer M Charlton-Ouw, MD FACS; University of Texas Health Science Center, Department of Cardiothoracic and Vascular Surgery, UT Medical School at Houston

  Study Documents (Full-Text)

Documents provided by Kristofer Charlton-Ouw, The University of Texas Health Science Center, Houston:

Study Protocol and Statistical Analysis Plan  [PDF] September 12, 2016

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sandhu HK, Miller CC 3rd, Tanaka A, Estrera AL, Charlton-Ouw KM. Effectiveness of Standard Local Anesthetic Bupivacaine and Liposomal Bupivacaine for Postoperative Pain Control in Patients Undergoing Truncal Incisions: A Randomized Clinical Trial. JAMA Netw Open. 2021 Mar 1;4(3):e210753. doi: 10.1001/jamanetworkopen.2021.0753.

• Responsible Party: Kristofer Charlton-Ouw, Associate Professor, Department of Cardiothoracic and Vascular Surgery, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT02111746
• Obsolete Identifiers: NCT02474472
• Other Study ID Numbers: CTVS-KC02; HSC-MS-13-0620 ( Other Identifier: UTHSC IRB )
• First Posted: April 11, 2014
• Results First Posted: October 16, 2018
• Last Update Posted: October 16, 2018
• Last Verified: September 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Kristofer Charlton-Ouw, The University of Texas Health Science Center, Houston:

Postoperative pain; sternotomy; laparotomy; thoracotomy; mini-thoracotomy; truncal surgical incisions; local anaesthetics; bupivacaine

Additional relevant MeSH terms:

Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pain; Neurologic Manifestations; Bupivacaine; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents