Abdominal SurgeryPhase 3CLEVELANDNCT04685876
Comparing TAP Blocks Bupivacaine, and Placebo for Plane
A Phase 3 study testing Liposomal bupivacaine, Plain bupivacaine and Normal saline in people with Abdominal Surgery, run by Edward Mascha at 1 site in United States.
Trial summary
The study will prospectively compare the analgesic efficacy of TAP blocks with liposomal bupivacaine, plain bupivacaine, and placebo in patients who are scheduled for major abdominal surgery. The primary aim is to assess the duration of the local analgesia (determined by pinprick and cold) in all four quadrants. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Abdominal Surgery
- What is being tested?
- Liposomal bupivacaine, Plain bupivacaine and Normal saline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 285 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Jun 2021to 20 Feb 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent;
- 18-85 years old;
- ASA Physical Status 1-3;
- Scheduled for elective open or laparoscopic-assisted abdominal surgery;
- Anticipated hospitalization of at least three nights;
- Expected requirement for parenteral opioids for at least 72 hours for postoperative pain;
- Able to use IV PCA systems.
Who cannot join
- Hepatic disease, e.g. twice the normal levels of liver enzymes;
- Kidney disease, e.g. twice the normal level of serum creatinine;
- Bupivacaine sensitivity or known allergy;
- Women who are pregnant or breastfeeding;
- Anticoagulants considered to be a contraindication for TAP blocks;
- Surgeries with high port sites;
- Weight <50 kg.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparison of Liposomal Bupivacaine, Plain Bupivacaine, and Placebo for Transversus Abdominis Plane Blocks: A Randomized, Blinded Trial
The study will prospectively compare the analgesic efficacy of TAP blocks with liposomal bupivacaine, plain bupivacaine, and placebo in patients who are scheduled for major abdominal surgery. The primary aim is to assess the duration of the local analgesia (determined by pinprick and cold) in all four quadrants. Comparing opioid consumption and pain scores is a secondary aim. All aims will be assessed over 72 hours or the duration of hospitalization if shorter.
Read the detailed description
The investigators propose a randomized double-blind trial comparing TAP blocks with liposomal bupivacaine, plain bupivacaine, and placebo in patients having elective abdominal surgery.
After eligibility is confirmed, patients will receive complete information about the study both verbally and in writing. Informed consent will be obtained from the patients prior to randomization and study-specific procedures.
Randomization will be based on computer-generated codes and use random-sized blocks. Allocations will be concealed until the morning of surgery where they will be provided by a web-based system. Randomization will be stratified by study site and chronic opioid use, defined by opioid use for more than 30 consecutive days within three preoperative months, at a daily dose of 15 mg or more of morphine or equivalent. Randomization will also be stratified according to anticipated type of surgery (open vs. laparoscopic-assisted). Clinicians doing the blocks will not be involved in data collection and all the evaluators will be blinded to group allocations.
All blocks will be performed preoperatively or after induction of anesthesia by attending anesthesiologists or regional anesthesia fellows who are experienced in TAP blocks. Premedication will be administered at the discretion of the attending anesthesiologist and standard monitors will be used. Patients will be given 1 g oral acetaminophen an hour before surgery, and an additional 500 mg every 6 hours for 72 hours after surgery starting with oral intake.
Patients will be randomly assigned to: 1) 4-quadrant TAP block with liposomal bupivacaine; 2) 4-quadrant TAP block with plain bupivacaine; or, 3) placebo (normal saline). An in-plane ultrasound will be guide TAP blocks. Two subcostal injections will be applied by placing the probe midline and then moving lateral along the subcostal margin identifying area between the rectus abdominis sheath and the transversus abdominis muscle. The lateral two TAP block injections will be applied in the midaxillary line between the thoracic cage and iliac crest between external oblique and transversus abdominis muscles. Once the target area is positioned, the following injections will be given, based on randomization:
Liposomal bupivacaine. 40 ml of plain bupivacaine 0.25% will be mixed with 20 ml liposomal bupivacaine and 20 ml of saline. 20 ml of the mix will be injected at each location of the 4-quadrant TAP block.
Plain bupivacaine group. 50 ml of plain bupivacaine 0.5% will be combined with 30 ml of normal saline making a total of 80 ml. 20 ml will be injected at each location of the 4-quadrant TAP block.
Placebo group; patients will receive total of 80 ml of normal saline, injected 20 ml in each of the four-quadrant sites.
General anesthesia will be induced using propofol or etomidate, fentanyl, and rocuronium to facilitate intubation. Anesthesia will be maintained with sevoflurane or isoflurane, along with opioids and muscle relaxants as clinically indicated. However, intraoperative analgesic use will be limited to fentanyl, a short-acting opioid.
Postoperatively, patients will be given intravenous patient-controlled analgesia and nurses will be free to give additional opioid as clinically indicated. Hydromorphone will be the default drug, but fentanyl will be substituted if necessary. Clinicians blinded to trial drug will adjust analgesic management as necessary in an effort to keep verbal response pain scores (details below) <4 points on a 0-10 scale, with 10 being worst pain. When patients no longer need PCA, they will be switched to as-needed hydromorphone or fentanyl.
A single dose of dexamethasone (4-8 mg) will be permitted for PONV prophylaxis, and inhaled steroids will be permitted as necessary to treat reactive airway disease. The use of non-steroidal anti-inflammatory drugs and gabapentinoids will be allowed as part of the ERAS approach (enhanced recovery after surgery) according to hospital's clinical practice. Other opioid-sparing medications such as ketamine and lidocaine patches will not be permitted through the initial 72 postoperative hours.
Patients will be allowed to receive prophylactic anti-emetic (first choice ondansetron) intraoperatively based on the risk assessment for nausea and vomiting. Postoperative anti-emetics for symptomatic treatment will also be allowed; again ondansetron will be the first choice.
- Conditions
- Abdominal Surgery
- Being tested
- Liposomal bupivacaine, Plain bupivacaine, Normal saline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liposomal bupivacaineDrug
4-quadrant TAP block with liposomal bupivacaine
Plain bupivacaineDrug
4-quadrant TAP block with plain bupivacaine
Normal salineDrug
placebo (normal saline).
| Study group | Role | What they receive |
|---|---|---|
| liposomal bupivacaine | Active comparator | 40 ml of plain bupivacaine 0.25% will be mixed with 20 ml liposomal bupivacaine and 20 ml of saline. 20 ml of the mix will be injected at each location of the 4-quadrant TAP block. Receives: Drug: Liposomal bupivacaine |
| plain bupivacaine | Active comparator | 50 ml of plain bupivacaine 0.5% will be combined with 30 ml of normal saline making a total of 80 ml. 20 ml will be injected at each location of the 4-quadrant TAP block. Receives: Drug: Plain bupivacaine |
| Normal Saline | Placebo comparator | patients will receive total of 80 ml of normal saline, injected 20 ml in each of the four-quadrant sites. Receives: Drug: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Opioids During Postoperative 24 Hours
Opioid consumption, measured in morphine milligram equivalents, during the first 24 hours of surgery
Measured: Postoperative 24 hours
Total Opioid Consumption During Postoperative 24 to 48 Hours
Total opioid consumption, in morphine milligram, equivalents, during postoperative 24 to 48 hours.
Measured: Postoperative 24 to 48 hours
Secondary outcomes (3)
Time to Return of Sensation
The investigator evaluate when patients feels both ice and pinprick in at least 6 of the 8 designated test locations, or 75% of the covered points if the TAP block did not initially cover all eight locations. The outcome is time (days) until sensation is recovered in 75% of the covered points.
Measured: 72 hours
Pain Scores During Postoperative 72 Hours
Pain scores measured using the numeric rating scale (NRS) going from 0 to 10, with 0 representing least pain and 10 representing most pain.
Measured: Postoperative 72 hours
Total Opioid Consumption (Postoperative 48 to 72 Hours)
Total opioid consumption, in morphine milligram equivalents, during postoperative 48 to 72 hours.
Measured: Postoperative 48 to 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2020
- Study start4 Jun 2021
- Primary completion20 Feb 2024
- Study completion20 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Abdominal SurgeryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 285 participants (actual)
Sponsor and investigators
- Lead sponsor
- Edward Mascha
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Edward Mascha, The Cleveland Clinic
- Investigators
- Alparslan Turan, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04685876
- Sponsor's protocol ID
- 20-790
- Acronym
- CLEVELAND
- Status last verified
- Aug 2025
- First submitted
- 22 Dec 2020
- Last updated
- 27 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Turan A, Ali Sakr Esa W, Brooker J, Rosen MJ, Ekrami E, Tok Cekmecelioglu B, Nair H, Al Jarkas A, Shah K, Mueller C, Valente M, El Hage Chehade N, Sessler DI; CLEVELAND Trial Group. Liposomal Bupivacaine, Plain Bupivacaine, and Saline for Transversus Abdominis Plane Blocks: The CLEVELAND Randomized Trial. Anesthesiology. 2026 Mar 1;144(3):546-558. doi: 10.1097/ALN.0000000000005869. Epub 2025 Dec 1.
PubMed 41329063
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Liposomal Bupivacaine, Plain Bupivacaine, and Placebo for Transversus Abdominis Plane Blocks: A Randomized, Blinded Trial
- ClinicalTrials.gov ID
- NCT04685876
- Acronym / sponsor ID
- CLEVELAND / 20-790
- Conditions
- Abdominal Surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 285 participants (actual)
- Lead sponsor
- Edward MaschaUniversity, hospital or other
- Study start
- 4 Jun 2021 (actual)
- Primary completion
- 20 Feb 2024 (actual)
- Study completion
- 20 Feb 2024 (actual)
- First posted
- 28 Dec 2020 (actual)
- Results
- Posted 7 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study will prospectively compare the analgesic efficacy of TAP blocks with liposomal bupivacaine, plain bupivacaine, and placebo in patients who are scheduled for major abdominal surgery. The primary aim is to assess the duration of the local analgesia (determined by pinprick and cold) in all four quadrants. Comparing opioid consumption and pain scores is a secondary aim. All aims will be assessed over 72 hours or the duration of hospitalization if shorter.
Detailed description
The investigators propose a randomized double-blind trial comparing TAP blocks with liposomal bupivacaine, plain bupivacaine, and placebo in patients having elective abdominal surgery.
After eligibility is confirmed, patients will receive complete information about the study both verbally and in writing. Informed consent will be obtained from the patients prior to randomization and study-specific procedures.
Randomization will be based on computer-generated codes and use random-sized blocks. Allocations will be concealed until the morning of surgery where they will be provided by a web-based system. Randomization will be stratified by study site and chronic opioid use, defined by opioid use for more than 30 consecutive days within three preoperative months, at a daily dose of 15 mg or more of morphine or equivalent. Randomization will also be stratified according to anticipated type of surgery (open vs. laparoscopic-assisted). Clinicians doing the blocks will not be involved in data collection and all the evaluators will be blinded to group allocations.
All blocks will be performed preoperatively or after induction of anesthesia by attending anesthesiologists or regional anesthesia fellows who are experienced in TAP blocks. Premedication will be administered at the discretion of the attending anesthesiologist and standard monitors will be used. Patients will be given 1 g oral acetaminophen an hour before surgery, and an additional 500 mg every 6 hours for 72 hours after surgery starting with oral intake.
Patients will be randomly assigned to: 1) 4-quadrant TAP block with liposomal bupivacaine; 2) 4-quadrant TAP block with plain bupivacaine; or, 3) placebo (normal saline). An in-plane ultrasound will be guide TAP blocks. Two subcostal injections will be applied by placing the probe midline and then moving lateral along the subcostal margin identifying area between the rectus abdominis sheath and the transversus abdominis muscle. The lateral two TAP block injections will be applied in the midaxillary line between the thoracic cage and iliac crest between external oblique and transversus abdominis muscles. Once the target area is positioned, the following injections will be given, based on randomization:
Liposomal bupivacaine. 40 ml of plain bupivacaine 0.25% will be mixed with 20 ml liposomal bupivacaine and 20 ml of saline. 20 ml of the mix will be injected at each location of the 4-quadrant TAP block.
Plain bupivacaine group. 50 ml of plain bupivacaine 0.5% will be combined with 30 ml of normal saline making a total of 80 ml. 20 ml will be injected at each location of the 4-quadrant TAP block.
Placebo group; patients will receive total of 80 ml of normal saline, injected 20 ml in each of the four-quadrant sites.
General anesthesia will be induced using propofol or etomidate, fentanyl, and rocuronium to facilitate intubation. Anesthesia will be maintained with sevoflurane or isoflurane, along with opioids and muscle relaxants as clinically indicated. However, intraoperative analgesic use will be limited to fentanyl, a short-acting opioid.
Postoperatively, patients will be given intravenous patient-controlled analgesia and nurses will be free to give additional opioid as clinically indicated. Hydromorphone will be the default drug, but fentanyl will be substituted if necessary. Clinicians blinded to trial drug will adjust analgesic management as necessary in an effort to keep verbal response pain scores (details below) <4 points on a 0-10 scale, with 10 being worst pain. When patients no longer need PCA, they will be switched to as-needed hydromorphone or fentanyl.
A single dose of dexamethasone (4-8 mg) will be permitted for PONV prophylaxis, and inhaled steroids will be permitted as necessary to treat reactive airway disease. The use of non-steroidal anti-inflammatory drugs and gabapentinoids will be allowed as part of the ERAS approach (enhanced recovery after surgery) according to hospital's clinical practice. Other opioid-sparing medications such as ketamine and lidocaine patches will not be permitted through the initial 72 postoperative hours.
Patients will be allowed to receive prophylactic anti-emetic (first choice ondansetron) intraoperatively based on the risk assessment for nausea and vomiting. Postoperative anti-emetics for symptomatic treatment will also be allowed; again ondansetron will be the first choice.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| liposomal bupivacaine | Active comparator | Drug: Liposomal bupivacaine40 ml of plain bupivacaine 0.25% will be mixed with 20 ml liposomal bupivacaine and 20 ml of saline. 20 ml of the mix will be injected at each location of the 4-quadrant TAP block. |
| plain bupivacaine | Active comparator | Drug: Plain bupivacaine50 ml of plain bupivacaine 0.5% will be combined with 30 ml of normal saline making a total of 80 ml. 20 ml will be injected at each location of the 4-quadrant TAP block. |
| Normal Saline | Placebo comparator | Drug: Normal salinepatients will receive total of 80 ml of normal saline, injected 20 ml in each of the four-quadrant sites. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Written informed consent;
- 18-85 years old;
- ASA Physical Status 1-3;
- Scheduled for elective open or laparoscopic-assisted abdominal surgery;
- Anticipated hospitalization of at least three nights;
Key exclusion criteria (7 listed)
- Hepatic disease, e.g. twice the normal levels of liver enzymes;
- Kidney disease, e.g. twice the normal level of serum creatinine;
- Bupivacaine sensitivity or known allergy;
- Women who are pregnant or breastfeeding;
- Anticoagulants considered to be a contraindication for TAP blocks;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liposomal bupivacaine4-quadrant TAP block with liposomal bupivacaine | Drug | liposomal bupivacaine |
| Plain bupivacaine4-quadrant TAP block with plain bupivacaine | Drug | plain bupivacaine |
| Normal salineplacebo (normal saline). | Drug | Normal Saline |
Primary outcome
Total Opioids During Postoperative 24 Hours
Time frame: Postoperative 24 hours
Opioid consumption, measured in morphine milligram equivalents, during the first 24 hours of surgery
Total Opioid Consumption During Postoperative 24 to 48 Hours
Time frame: Postoperative 24 to 48 hours
Total opioid consumption, in morphine milligram, equivalents, during postoperative 24 to 48 hours.
3 secondary outcomes
Time to Return of Sensation
Time frame: 72 hours
Pain Scores During Postoperative 72 Hours
Time frame: Postoperative 72 hours
Total Opioid Consumption (Postoperative 48 to 72 Hours)
Time frame: Postoperative 48 to 72 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41329063Turan A, Ali Sakr Esa W, Brooker J, Rosen MJ, Ekrami E, Tok Cekmecelioglu B, Nair H, Al Jarkas A, Shah K, Mueller C, Valente M, El Hage Chehade N, Sessler DI; CLEVELAND Trial Group. Liposomal Bupivacaine, Plain Bupivacaine, and Saline for Transversus Abdominis Plane Blocks: The CLEVELAND Randomized Trial. Anesthesiology. 2026 Mar 1;144(3):546-558. doi: 10.1097/ALN.0000000000005869. Epub 2025 Dec 1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alparslan Turan, MD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Liposomal bupivacaine, Plain bupivacaine and Normal saline in people with Abdominal Surgery, run by Edward Mascha 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 7 inclusion and 7 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 27 Aug 2025. 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. Some participants in this study may receive a placebo. 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?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Total Opioids During Postoperative 24 Hours (time frame: Postoperative 24 hours). The study lists 2 primary outcomes in all. 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 NCT04685876, which also lists 1 linked publication.
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 27 Aug 2025.