Long-term Outcomes of Breast Cancer Patients After Wound Infiltration Analgesia

NCT05829707 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: OsijekUH21
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

Brief Summary

In the study that was conducted from 05.01.2009 - 31.12.2012. 120 patients were examined. By drawing random numbers, the patients were randomized into 3 groups for postoperative analgesia:

1. 1.Diclofenac 2 mg/kg/day - control,
2. 2.Wound infiltration via wound catheter with catheter tip placed in the axilla, 3\*0.5 mg/kg 0.5% levobupivacaine bolus dose.
3. 3.0.05 mg/kg/h 0.5% levobupivacaine continuously via wound infiltration catheter with catheter tip placed in the axilla. The drug was delivered using a PCA pump for 24 hours.

Conditions

Postoperative Analgesia; Hand Strength; Health Related Quality of Life; Chronic Shoulder Pain; Breast Cancer Female; Surgical Wound Infiltration; Lymph Node Dissection

Keywords

Acute Postoperative Pain; Breast Cancer; Postoperative analgesia; Patient-Controlled Analgesia; Levobupivacaine; Diclofenac; Hand Grip Strength; Quality of life; Treatment Outcome

Outcome Measures

Primary Outcomes (4)

• Postoperative analgesia

  Pain after mastectomy was evaluated by self-reports from patients using a Visual Analog Scale (VAS) from 0 - no pain up to 10 - the worst pain imaginable.

  from 1-4 days postoperative, day of surgery is day 1

• Hand grip strength

  Hand grip strength (HGS) was measured preoperatively, 4 days after surgery and at follow-up after 1 year, using a handheld dynamometer (Dynatest®, Rud. Reister Gmbh\&CaKG, Jungingen, Germany) and expressed in bars. Mean expected normal values for female patients are in the range between 0.4-0.6 bar.

  Before surgery, on day 4 after surgery, and one year after surgery

• Shoulder disability

  Shoulder pain was assessed using the Shoulder Disability Questionnaire (SDQ), and shoulder pain was assessed in 16 typical situations such as writing, opening a door, sleeping on the operated side, or carrying a load. The maximal score was all positive ( 16 in 16, 100%), suggesting that pain was present in all 16 clinical situations, and the minimum score is 0 (0 positive responses /16 situations, 0% - no disability in any situation.

  Before surgery and after one year at surgical control.

• Health related quality of life

  Health-related quality of life was assessed using the Croatian version of the SF-36 questionnaire. There were eight domains examined: physical health, role limitation due to physical problems, pain, general health perception, energy / vitality, social functioning, limitations due to emotional problems, and general mental health. This instrument summarizes health perception from the patient's perspective. SF-36 scores range from 0 (worst) to 100 (best) (5).

  Before surgery and after one year at surgical control.

Secondary Outcomes (2)

• Long-term survival - 5 years after surgery

  Five years after surgery

• Long term survival - 10 years after surgery

  Ten years after surgery until data were collected

Study Arms (3)

Diclofenac

ACTIVE COMPARATOR

All patients underwent quadrantectomy or mastectomy with axillary lymph node dissection. They received diclofenac 2 x 75 mg intravenously on the first day after surgery. During the 3 subsequent days, from day 2 to day 4 postoperatively patients were given 3 x 50 mg diclofenac tablets orally. The medicine was delivered by the nurse, and the patients drank tablets in front of her.

Drug: Diclofenac Sodium

Levobupivacaine bolus analgesia

EXPERIMENTAL

Group Levobupivacaine Bolus received 0.5 mg/kg 0.5% Levobupivacaine HCl every 8 h via wound catheter. The dose of levobupivacaine was prescribed by the doctor and the drug was delivered by the nurse.

Drug: Levobupivacaine bolus analgesia

Levobupivacaine PCA group

EXPERIMENTAL

Group Levobupivacaine patient-controlled analgesia (PCA) received 0.05 mg/kg 0.5% Levobupivacaine HCl continuously via wound catheter delivered by CADD - Legacy® PCA Pump. These patients were allowed to add a dose of 7.5 mg 0.5% levobupivacaine in case of pain by pressing the patient's button on the PCA pump, with a lock-out period of 4 hours.

Drug: Levobupivacaine PCA group

Interventions

Diclofenac Sodium DRUG

A group of patients with breast cancer who were randomized to the diclofenac group by drawing random numbers was given 2 x 75 mg of drug IV on the first PO day and then 3 x 50 mg tablets orally for postoperative analgesia. All patients were assessed before the surgical procedure: hand grip strength, shoulder disability, and health-related quality of life were measured. Pain relief was assessed by the visual analog scale (VAS) from 0-10. Rescue analgesia was offered for pain \>4 on the VAS, meperidine 20-30 mg for VAS \>or = 4

Also known as: Nonsteroidal antiinflammatory drug

Diclofenac

Levobupivacaine bolus analgesia DRUG

The levobupivacaine dose was calculated by a doctor. A wound infiltration catheter was inserted at the end of the surgical procedure by a surgeon. A first dose of local anesthetic was delivered at the end of the surgical procedure to test catheter placement. Bolus doses of local anesthetics based on the patients' body weight were thereafter delivered by the nurse in 8 hours intervals. All patients were assessed before the surgical procedure and hand grip strength, shoulder disability, and health-related quality of life were measured. Pain relief was assessed by the visual analog scale (VAS) from 0-10. Rescue analgesia was offered for pain \>4 on the VAS, meperidine 20-30 mg for VAS \>or = 4.

Also known as: Postoperative wound infiltration with bolus applications of local anesthetic, Chirocaine 0.5%

Levobupivacaine bolus analgesia

Levobupivacaine PCA group DRUG

The levobupivacaine dose was calculated by a doctor. A wound infiltration catheter was inserted at the end of the surgical procedure by a surgeon. Levobupivacaine was delivered by PCA pump (CADD - Legacy® PCA Pump, Model 6300, Smiths Medical MD, Inc., St. Paul, USA). A drug delivery was started at the end of the surgical procedure. All patients were assessed before the surgical procedure: hand grip strength, shoulder disability, and health-related quality of life were measured. Pain relief was assessed by the visual analog scale (VAS) from 0-10. Rescue analgesia was offered for persisting pain \>4 on the VAS, and meperidine 20-30 mg for VAS \>or = 4.

Also known as: Postoperative continuous wound infiltration analgesia with local anesthetic, Chirocaine 0.5%

Levobupivacaine PCA group

Eligibility Criteria

• Age: 30 Years - 75 Years
• Gender Eligibility Details: Female breast cancer patients were included in the study
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Breast cancer patients whose disease requires axillary lymph node dissection
• who consented to participate in the study
• aged 30 - 75
• The patient is able to understand all three methods of analgesia
• Patients can receive any of the study drugs
• Able to understand and complete questionnaires on quality of life and shoulder pain

You may not qualify if:

• Age \<30 years - \>75 years
• Patients who refused to participate in the study (at any stage of the study)
• Patients who after histological analysis did not require axillary lymph node dissection
• Patients with known intolerance to study drugs
• Patients who unintentionally removed wound infiltration catheters.
• Patients who required surgical reintervention during the study period
• Patients having adverse reactions to any study drug.

Sponsors & Collaborators

• Osijek University Hospital: lead

Related Publications (9)

• Beguinot M, Monrigal E, Kwiatkowski F, Ginzac A, Joly D, Gayraud G, Le Bouedec G, Gimbergues P. Continuous Wound Infiltration With Ropivacaine After Mastectomy: A Randomized Controlled Trial. J Surg Res. 2020 Oct;254:318-326. doi: 10.1016/j.jss.2020.05.006. Epub 2020 Jun 5.

  PMID: 32512380 BACKGROUND

• Kaur U, Shamshery C, Agarwal A, Prakash N, Valiveru RC, Mishra P. Evaluation of postoperative pain in patients undergoing modified radical mastectomy with pectoralis or serratus-intercostal fascial plane blocks. Korean J Anesthesiol. 2020 Oct;73(5):425-433. doi: 10.4097/kja.20159. Epub 2020 Sep 24.

  PMID: 32987492 BACKGROUND

• Li R, Xiao C, Liu H, Huang Y, Dilger JP, Lin J. Effects of local anesthetics on breast cancer cell viability and migration. BMC Cancer. 2018 Jun 19;18(1):666. doi: 10.1186/s12885-018-4576-2.

  PMID: 29914426 BACKGROUND

• Chen JL, Liu ST, Huang SM, Wu ZF. Apoptosis, Proliferation, and Autophagy Are Involved in Local Anesthetic-Induced Cytotoxicity of Human Breast Cancer Cells. Int J Mol Sci. 2022 Dec 7;23(24):15455. doi: 10.3390/ijms232415455.

  PMID: 36555096 BACKGROUND

• Castelli V, Piroli A, Marinangeli F, d'Angelo M, Benedetti E, Ippoliti R, Zis P, Varrassi G, Giordano A, Paladini A, Cimini A. Local anesthetics counteract cell proliferation and migration of human triple-negative breast cancer and melanoma cells. J Cell Physiol. 2020 Apr;235(4):3474-3484. doi: 10.1002/jcp.29236. Epub 2019 Sep 20.

  PMID: 31541469 BACKGROUND

• Kwakye AK, Kampo S, Lv J, Ramzan MN, Richard SA, Falagan AA, Agudogo J, Atito-Narh E, Yan Q, Wen QP. Levobupivacaine inhibits proliferation and promotes apoptosis of breast cancer cells by suppressing the PI3K/Akt/mTOR signalling pathway. BMC Res Notes. 2020 Aug 17;13(1):386. doi: 10.1186/s13104-020-05191-2.

  PMID: 32807213 BACKGROUND

• Klein I, Kalichman L, Chen N, Susmallian S. Effect of physical activity levels on oncological breast surgery recovery: a prospective cohort study. Sci Rep. 2021 May 17;11(1):10432. doi: 10.1038/s41598-021-89908-8.

  PMID: 34002007 BACKGROUND

• Meerkerk CDA, Chargi N, de Jong PA, van den Bos F, de Bree R. Sarcopenia measured with handgrip strength and skeletal muscle mass to assess frailty in older patients with head and neck cancer. J Geriatr Oncol. 2021 Apr;12(3):434-440. doi: 10.1016/j.jgo.2020.10.002. Epub 2020 Oct 13.

  PMID: 33067163 BACKGROUND

• Glavas Tahtler J, Djapic D, Neferanovic M, Miletic J, Milosevic M, Kralik K, Neskovic N, Tomas I, Mesaric D, Marjanovic K, Rajc J, Orkic Z, Cicvaric A, Kvolik S. Long-Term Outcomes of Breast Cancer Patients Receiving Levobupivacaine Wound Infiltration or Diclofenac for Postoperative Pain Relief. Pharmaceutics. 2023 Aug 23;15(9):2183. doi: 10.3390/pharmaceutics15092183.

  PMID: 37765154 DERIVED

MeSH Terms

Conditions

Pain, Postoperative; Breast Neoplasms

Interventions

Diclofenac; Anti-Inflammatory Agents, Non-Steroidal; Anesthetics, Local

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Anti-Inflammatory Agents; Therapeutic Uses; Antirheumatic Agents; Anesthetics; Central Nervous System Depressants; Central Nervous System Agents

Study Officials

• Josipa Glavas Tahtler, MD

  Department of Anaesthesiology, Resuscitation and ICU, Osijek University Hospital,

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: On the one-year control examination, the investigator was blinded on the type of postoperative analgesia
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2023
• First Posted: April 26, 2023
• Study Start: January 5, 2009
• Primary Completion: December 31, 2012
• Study Completion: April 5, 2023
• Last Updated: April 28, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share