Intraoperative Ketamine on Chronic Pain After Mastectomy

NCT02729805 | Suspended Phase 4 DMC

• 1 other identifier: UW15-079
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 1

Brief Summary

Preventive analgesia is when an administered analgesic drug provides reduction in pain beyond its duration of action. This can be used to reduce acute postoperative pain and prevent occurrence of chronic post-surgical pain. According to the International Association for the Study of Pain (IASP), chronic pain can be defined as pain that persisted beyond the time of normal tissue healing (usually 3 months) and that was not related to other causes. Mastectomy is associated with a high incidence of chronic post-surgical pain. Breast cancer is the most common malignancy affecting females around the world. Many undergo mastectomy as part of curative treatment. However, a significant proportion of patients experience chronic post-surgical pain. This results in significant negative impact on physical, psychological and social wellbeing. Ketamine is an intravenous anaesthetic drug with analgesic effects. It can be used to treat both acute and chronic pain. A recent meta-analysis of different surgeries showed that patients receiving ketamine had a modest but statistically significant reduction in incidence of chronic post-surgical pain. In a small sample single dose pilot study, patients given low dose intravenous ketamine intraoperatively had a statistically non-significant reduction in incidence of pain around the surgical scar at three months after radical mastectomy. Randomized control trials with larger sample sizes are needed to determine the effectiveness and optimal dosing regime of ketamine for reduction of chronic post-mastectomy pain. It is therefore hypothesized that intravenous ketamine given intraoperatively will reduce the incidence and severity of chronic pain after modified radical mastectomy. A double blind randomized controlled trial comparing placebo group with two different doses of ketamine is proposed. The mechanism of action of ketamine in reducing pain is complex and multiple. How ketamine can prevent and reduce chronic pain is unknown. Ketamine has been shown to reduce immediate gene expression at site of mechanical injury. Transient Receptor Potential Vanilloid 1 (TRPV1) and Transient Receptor Ankyrin 1 (TRPA1) are receptors shown to mediate acute and chronic pain. Ketamine, shown to affect gene expression, may alter the expression of TRPV1 and TRPA1 via epigenetic mechanisms.

Conditions

Chronic Pain

Keywords

ketamine; chronic pain; mastectomy; acute pain

Outcome Measures

Primary Outcomes (1)

• Severity of chronic pain

  Determine the severity using numerical rating scale

  At postoperative 3 months

Secondary Outcomes (1)

• Incidence of neuropathic pain

  At postoperative 3 months

Study Arms (3)

Saline

PLACEBO COMPARATOR

A syringe of 50 ml 0.9% normal saline will be prepared as placebo for infusion and a syringe of 10ml 0.9% normal saline for bolus injection.

Drug: Saline

Ketamine 0.5mg/kg

ACTIVE COMPARATOR

A bolus injection of intravenous ketamine at a dose of 0.5mg/kg during anaesthetic induction before skin incision followed by 0.25mg/kg/hr intravenous ketamine infusion during the operation.

Drug: Ketamine 0.5mg/kg

Ketamine 0.75mg/kg

EXPERIMENTAL

A bolus injection of intravenous ketamine at a dose of 0.75mg/kg during anaesthetic induction before skin incision followed by 0.5mg/kg/hr intravenous ketamine infusion during the operation.

Drug: Ketamine 0.75mg/kg

Interventions

Saline DRUG

10ml bolus injection of saline followed by intravenous infusion of saline during the operation

Also known as: Control group

Saline

Ketamine 0.5mg/kg DRUG

0.5mg/kg intravenous ketamine injection followed by 0.25mg/kg/hr intravenous ketamine infusion during the operation

Also known as: Group K1

Ketamine 0.5mg/kg

Ketamine 0.75mg/kg DRUG

0.75mg/kg intravenous ketamine injection followed by 0.5mg/kg/hr intravenous ketamine infusion during the operation

Also known as: Group K2

Ketamine 0.75mg/kg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• the American Society of Anesthesiologists adopted physical status classification system (ASA) I-III
• Age 18-80 years old
• Scheduled for 1) modified radical mastectomy (including axillary lymph node dissection) and 2) mastectomy with sentinel lymph node (without axillary dissection). These are the common surgical treatments for breast cancer.

You may not qualify if:

• Radical mastectomy, wide local excision or lumpectomy
• Known allergy to opioids, local anaesthetic drugs, non-steroidal anti-inflammatory drugs (NSAIDS) including COX-2 inhibitors
• History of chronic pain
• Alcohol or drug abuse
• Impaired renal function, defined as preoperative serum creatinine level over 120 micromol/L
• Pre-existing neurological or muscular disorders
• Psychiatric illness
• Impaired or retarded mental state
• Not self ambulatory before operation
• Difficulties in using patient controlled analgesia (PCA)
• Pregnancy
• Local infection
• Patient refusal

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

The University of Hong Kong

Hong Kong, 0000, Hong Kong

Location

MeSH Terms

Conditions

Chronic Pain; Acute Pain

Interventions

Sodium Chloride; Control Groups; Ketamine

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Stanley SC Wong, MBBS

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: June 28, 2015
• First Posted: April 6, 2016
• Study Start: August 18, 2015
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2024
• Last Updated: May 10, 2023

Record last verified: 2023-05

Locations

HK (1)