Breast CancerPhase 2NCT02525718
Selective Intraoperative Administration of Local Anesthesia in Breast Reconstruction
A Phase 2 study testing Saline and 0.25 % bupivacaine (2.5 mg/ml) w/ 1:100,000 epinephrine & 4 mg dexamethasone in people with Breast Cancer, run by Northwestern University at 1 site in United States.
Trial summary
Subjects are being asked to participate in this study because they will be undergoing unilateral (one) or bilateral (two) mastectomy surgery with immediate reconstruction involving insertion of a tissue expander. Read more about this study
- Who is it for?
- Ages 18 to 79 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Saline and 0.25 % bupivacaine (2.5 mg/ml) w/ 1:100,000 epinephrine & 4 mg dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 47 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2015to Mar 2017
- Phase
- Phase 2
- 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 79 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who undergo mastectomy surgery with immediate reconstruction involving insertion of a tissue expander performed by the principal investigator beginning from the time of study approval until study enrollment is complete.
Who cannot join
- Patients under the age of 18, or over the age of 79
- Allergy to local anesthetics or corticosteroids
- Patients with history of chronic pain or with chronic use of opioid analgesics
- Patients with history of lung disease or prior anterior thoracotomy or median sternotomy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Does Selective Intraoperative Administration of Local Anesthesia in Breast Reconstruction Reduce Postoperative Pain and Opioid Requirement?: A Prospective Double-Blinded Randomized Controlled Trial
Subjects are being asked to participate in this study because they will be undergoing unilateral (one) or bilateral (two) mastectomy surgery with immediate reconstruction involving insertion of a tissue expander.
Read the detailed description
One in eight women will develop breast cancer in her lifetime, and many of these women undergo mastectomy followed by breast reconstruction by insertion of a tissue expander below the pectoralis major muscle. Women undergoing breast reconstruction have been shown to have a significantly higher level of acute postoperative pain and postoperative narcotic requirement compared to women who undergo mastectomy alone without reconstruction. In addition to the inherently worthwhile end of providing patient comfort in the immediate postoperative period, decreased narcotic use carries with it the potential benefit of decreasing the incidence of other adverse effects such as nausea, vomiting, allergic reaction, and respiratory depression.
Importantly, the intensity of pain in the immediate postoperative period has been implicated as an important factor predisposing patients to the development of chronic postoperative pain. Chronic pain following mastectomy is a significant and disabling problem, affecting up to 49% of patients in some series. Though breast reconstruction has been shown not to be an independent predictor of the development of chronic breast pain, improved control of acute pain in the immediate postoperative period carries significant promise in decreasing the incidence of this disabling condition for all breast cancer survivors treated with mastectomy. In addition, improving management of acute postoperative pain can shorten hospital stay, expedite return to daily normal activities and increase patient satisfaction.
A variety of other adjuncts for pain control have been attempted in studies of variable methodological rigor, including injection of botulinum toxin into the pectoralis muscle, indwelling pain catheters, paravertebral blocks under ultrasound guidance, or simple irrigation of the general area of dissection during breast surgery with a solution containing local anesthestic. While each of these adjuncts has demonstrated some success, none has been widely adopted. Problems with these methods include cost, risk of adverse events, as well as anatomically incomplete or non-selective application.
During mastectomy all breast tissue is removed, leaving the patient with denervated skin flaps. For breast reconstruction, a tissue expander is placed in a subpectoral pocket dissected between the pectoralis major and minor muscles. At the end of the procedure the pectoralis major muscle is placed under variable degree of tension depending on the amount of fluid placed inside the expander. This muscle stretch believed to be at least partially responsible for postoperative pain. In addition cut nerve endings in the superficial fascia likely contribute as well. The anatomy of nerves supplying the breast and involved muscles are well-described in rigorous cadaver studies.
In this study we hypothesize that performing a block of the intercostal nerves responsible for innervating the breast tissue and skin and the pectoral nerves innervating the pectoralis major muscle should optimize immediate postoperative pain control in this patient population. Of adjuncts described in the literature, paravertebral blocks are the most anatomically targeted, but drawbacks include the need for a separate procedure preoperatively while the patient is awake by an anesthesiologist with facility performing these blocks as well as the risk of pneumothorax. Advantages of our proposed method include lack of pain as the patient is asleep, easy and speed of application, a decreased risk of pneumothorax as the injections are under direct visualization, as well as a decrease in cost and improved efficiency as the only a single provider (i.e. the operative surgeon) is required. Precedent for our technique has been described in the context of breast augmentation and breast lift, with a favorable safety profile and providing adequate analgesia to perform these procedures without the use of a general anesthetic.
- Conditions
- Breast Cancer
- Being tested
- Saline, 0.25 % bupivacaine (2.5 mg/ml) w/ 1:100,000 epinephrine & 4 mg dexamethasone
- Keywords
- Breast Reconstruction, Mastectomy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SalineDrug
Also called Sodium Chloride 0.9%
If randomized to this arm, subjects will receive an intraoperative injection of saline. (2.5 mg/ml)
0.25 % bupivacaine (2.5 mg/ml) w/ 1:100,000 epinephrine & 4 mg dexamethasoneDrug
Also called Bupivacaine
If randomized to this arm, subjects will receive a selective block with a local anesthetic solution containing 0.25 % bupivacaine.
(2.5 mg/ml) with 1:100,000 epinephrine and 4 mg dexamethasone intraoperatively.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Subjects will be randomly selected to receive saline (placebo), administered to the breast area to cover the intercostal nerves supplying the breast tissue during surgery. Receives: Drug: Saline |
| 0.25 % bupivacaine w/ epinephrine & 4mg dexamethasone | Active comparator | Subjects will be randomly selected to receive selective block with a local anesthetic solution containing 0.25 % bupivacaine (2.5 mg/ml) with 1:100,000 epinephrine and 4 mg dexamethasone. The injection will be performed in certain locations of the breast area to cover the intercostal nerves supplying the breast tissue.
Subjects will be randomly selected to receive the local anesthetic solution containing 0.25 % bupivacaine (2.5 mg/ml) with 1:100,000 epinephrine and 4 mg dexamethasoneadministered to the breast area to cover the intercostal nerves supplying the breast tissue during surgery. Receives: Drug: 0.25 % bupivacaine (2.5 mg/ml) w/ 1:100,000 epinephrine & 4 mg dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quality of Recovery Score
The primary outcome measure is a well-validated and widely used survey measuring the quality of recovery from anesthesia entitled the "Global 40 Item Quality of Recovery" survey. This is a 40 question survey administered to patients to allow them to rate their quality of recovery along a number of different dimensions, including emotional state, physical comfort, psychological support, physical independence, and pain. The score ranges from 40 to 200, with 40 representing a very poor overall quality of recovery and 200 representing the best possible recovery. The following reference explains the Global 40 Item Quality of Recovery survey in detail:
Myles, P.S., et al., Validity and reliability of a postoperative quality of recovery score: the QoR-40. Br J Anaesth, 2000. 84(1): p. 11-5.
PMID: 10740540
Measured: 24 hours post-operatively
Secondary outcomes (3)
Pain Score Using 10-point Visual Analog Scale (VAS)
A study-specific pain form was provided to the patient and nursing staff that consisted of standard visual analogue scale (VAS) for patients to rate their pain level. Pain level was rated as a categorical level from 0 to 10, in 1 unit increments, with 0 being "no pain at all" and 10 being "worst pain imaginable." Thus a total of 10 pain grades were possible.
Measured: 24 hrs
Opioid Consumption
Total opioid consumption in the first 24 hrs of recovery after surgery as measured in "morphine equivalents." This involves converting the dose of a non-morphine narcotic (e.g. IV hydromorphone or oral hydrocodone) into the equi-analgesic dose of morphine, so that the total amount of narcotic utilized by the patient can be compared. This is a standard technique for comparison utilized in the pain management literature.
Measured: 24 hrs
Length of Hospital Stay
Number of postoperative days patients stay in the hospital after surgery
Measured: 4 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2015 (estimated)
- Study startAug 2015
- Primary completionNov 2016
- Study completionMar 2017
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.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohammed Alghoul, Northwestern University
- Investigators
- Mohammed Alghoul, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02525718
- Sponsor's protocol ID
- STU00200903
- Status last verified
- Jul 2019
- First submitted
- 6 Jul 2015
- Last updated
- 14 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Selective Intraoperative Administration of Local Anesthesia in Breast Reconstruction Reduce Postoperative Pain and Opioid Requirement?: A Prospective Double-Blinded Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT02525718
- Acronym / sponsor ID
- STU00200903
- Conditions
- Breast Cancer
- Keywords
- Breast Reconstruction, Mastectomy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- Aug 2015 (actual)
- Primary completion
- Nov 2016 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 17 Aug 2015 (estimated)
- Results
- Posted 14 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Subjects are being asked to participate in this study because they will be undergoing unilateral (one) or bilateral (two) mastectomy surgery with immediate reconstruction involving insertion of a tissue expander.
Detailed description
One in eight women will develop breast cancer in her lifetime, and many of these women undergo mastectomy followed by breast reconstruction by insertion of a tissue expander below the pectoralis major muscle. Women undergoing breast reconstruction have been shown to have a significantly higher level of acute postoperative pain and postoperative narcotic requirement compared to women who undergo mastectomy alone without reconstruction. In addition to the inherently worthwhile end of providing patient comfort in the immediate postoperative period, decreased narcotic use carries with it the potential benefit of decreasing the incidence of other adverse effects such as nausea, vomiting, allergic reaction, and respiratory depression.
Importantly, the intensity of pain in the immediate postoperative period has been implicated as an important factor predisposing patients to the development of chronic postoperative pain. Chronic pain following mastectomy is a significant and disabling problem, affecting up to 49% of patients in some series. Though breast reconstruction has been shown not to be an independent predictor of the development of chronic breast pain, improved control of acute pain in the immediate postoperative period carries significant promise in decreasing the incidence of this disabling condition for all breast cancer survivors treated with mastectomy. In addition, improving management of acute postoperative pain can shorten hospital stay, expedite return to daily normal activities and increase patient satisfaction.
A variety of other adjuncts for pain control have been attempted in studies of variable methodological rigor, including injection of botulinum toxin into the pectoralis muscle, indwelling pain catheters, paravertebral blocks under ultrasound guidance, or simple irrigation of the general area of dissection during breast surgery with a solution containing local anesthestic. While each of these adjuncts has demonstrated some success, none has been widely adopted. Problems with these methods include cost, risk of adverse events, as well as anatomically incomplete or non-selective application.
During mastectomy all breast tissue is removed, leaving the patient with denervated skin flaps. For breast reconstruction, a tissue expander is placed in a subpectoral pocket dissected between the pectoralis major and minor muscles. At the end of the procedure the pectoralis major muscle is placed under variable degree of tension depending on the amount of fluid placed inside the expander. This muscle stretch believed to be at least partially responsible for postoperative pain. In addition cut nerve endings in the superficial fascia likely contribute as well. The anatomy of nerves supplying the breast and involved muscles are well-described in rigorous cadaver studies.
In this study we hypothesize that performing a block of the intercostal nerves responsible for innervating the breast tissue and skin and the pectoral nerves innervating the pectoralis major muscle should optimize immediate postoperative pain control in this patient population. Of adjuncts described in the literature, paravertebral blocks are the most anatomically targeted, but drawbacks include the need for a separate procedure preoperatively while the patient is awake by an anesthesiologist with facility performing these blocks as well as the risk of pneumothorax. Advantages of our proposed method include lack of pain as the patient is asleep, easy and speed of application, a decreased risk of pneumothorax as the injections are under direct visualization, as well as a decrease in cost and improved efficiency as the only a single provider (i.e. the operative surgeon) is required. Precedent for our technique has been described in the context of breast augmentation and breast lift, with a favorable safety profile and providing adequate analgesia to perform these procedures without the use of a general anesthetic.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: SalineSubjects will be randomly selected to receive saline (placebo), administered to the breast area to cover the intercostal nerves supplying the breast tissue during surgery. |
| 0.25 % bupivacaine w/ epinephrine & 4mg dexamethasone | Active comparator | Drug: 0.25 % bupivacaine (2.5 mg/ml) w/ 1:100,000 epinephrine & 4 mg dexamethasoneSubjects will be randomly selected to receive selective block with a local anesthetic solution containing 0.25 % bupivacaine (2.5 mg/ml) with 1:100,000 epinephrine and 4 mg dexamethasone. The injection will be performed in certain locations of the breast area to cover the intercostal nerves supplying the breast tissue. Subjects will be randomly selected to receive the local anesthetic solution containing 0.25 % bupivacaine (2.5 mg/ml) with 1:100,000 epinephrine and 4 mg dexamethasoneadministered to the breast area to cover the intercostal nerves supplying the breast tissue during surgery. |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients who undergo mastectomy surgery with immediate reconstruction involving insertion of a tissue expander performed by the principal investigator beginning from the time of study approval until study enrollment is complete.
Key exclusion criteria (4 listed)
- Patients under the age of 18, or over the age of 79
- Allergy to local anesthetics or corticosteroids
- Patients with history of chronic pain or with chronic use of opioid analgesics
- Patients with history of lung disease or prior anterior thoracotomy or median sternotomy
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 |
|---|---|---|
| SalineAlso: Sodium Chloride 0.9%If randomized to this arm, subjects will receive an intraoperative injection of saline. (2.5 mg/ml) | Drug | Placebo |
| 0.25 % bupivacaine (2.5 mg/ml) w/ 1:100,000 epinephrine & 4 mg dexamethasoneAlso: BupivacaineIf randomized to this arm, subjects will receive a selective block with a local anesthetic solution containing 0.25 % bupivacaine. (2.5 mg/ml) with 1:100,000 epinephrine and 4 mg dexamethasone intraoperatively. | Drug | 0.25 % bupivacaine w/ epinephrine & 4mg dexamethasone |
Primary outcome
Quality of Recovery Score
Time frame: 24 hours post-operatively
The primary outcome measure is a well-validated and widely used survey measuring the quality of recovery from anesthesia entitled the "Global 40 Item Quality of Recovery" survey. This is a 40 question survey administered to patients to allow them to rate their quality of recovery along a number of different dimensions, including emotional state, physical comfort, psychological support, physical independence, and pain. The score ranges from 40 to 200, with 40 representing a very poor overall quality of recovery and 200 representing the best possible recovery. The following reference explains the Global 40 Item Quality of Recovery survey in detail: Myles, P.S., et al., Validity and reliability of a postoperative quality of recovery score: the QoR-40. Br J Anaesth, 2000. 84(1): p. 11-5. PMID: 10740540
3 secondary outcomes
Pain Score Using 10-point Visual Analog Scale (VAS)
Time frame: 24 hrs
Opioid Consumption
Time frame: 24 hrs
Length of Hospital Stay
Time frame: 4 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Mohammed Alghoul, MD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Saline and 0.25 % bupivacaine (2.5 mg/ml) w/ 1:100,000 epinephrine & 4 mg dexamethasone in people with Breast Cancer, run by Northwestern University 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 1 inclusion and 4 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 14 Aug 2019. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 14 Aug 2019). 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?
Quality of Recovery Score (time frame: 24 hours post-operatively). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Aug 2019.