Clinical trial NCT05935059: The Efficacy of Tianeptine Versus Pregabalin on Acute and Chronic Post Mastectomy Pain After Breast Cancer Surgery.
Official title: Evaluation of the Efficacy of Perioperative Administration of Tianeptine Versus Pregabalin on Acute and Chronic Post Mastectomy Pain After Breast Cancer Surgery. A Double-Blinded Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Post-mastectomy Pain Syndrome
Keywords: Breast cancer
Post mastectomy pain
chronic pain
Lead sponsor: National Cancer Institute, Egypt
Sponsor class: OTHER
First posted: 2023-07-07
Enrollment: 90
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Breast cancer is the most common malignancy among females. Nearly 40% of breast surgery patients experience moderate to severe acute postoperative pain, with severe pain persisting for more than 6 months in almost 20-50% of patients (post mastectomy pain syndrome) which is defined according to International Association for the Study of Pain (IASP) as pain which persists more than 3 months after mastectomy/lumpectomy affecting the anterior thorax, axilla, and/or medial upper arm. Different pharmacological tools have been in use for either prevention or treatment of such refractory pain syndrome with variable efficacy. The aim of this study is to assess the efficacy of the perioperative use of Pregabalin versus Tianeptine on the emergence of PMPS in female patients undergoing MRM for breast cancer.

Detailed description: Breast cancer is the most common diagnosed malignancy among females and the 5th cause of cancer-related deaths with an estimated number of 2.3 million new cases and 685,000 deaths worldwide in 2020.

Different modalities are used for management of breast cancer including surgery, radiation therapy (RT), chemotherapy (CT), endocrine (hormone) therapy (ET), and targeted therapy. Modified Radical Mastectomy (MRM) is one of the main modalities of breast cancer treatment. It accounts for 31% of all breast surgeries. It has been reported that 40% of the females complain from moderate-to-severe pain in the immediate post-operative period after breast cancer surgery.

Acute post-mastectomy pain can cause adverse impacts on the patients as delayed discharge from post-operative recovery area, impairs pulmonary and immune functions, increases risk of ileus, thromboembolism, myocardial infarction and may lead to increased length of hospital stay. It is also an important factor leading to the development of chronic post mastectomy pain syndrome (PMPS) in almost half of the patients.

The International Association for the Study of Pain (IASP) defines PMPS as pain which persists more than 3 months after mastectomy that affects the anterior thorax, axilla, and/or medial upper arm. It is usually described as the feeling of burning, stabbing, and pulling around the treatment side. The underlying pathophysiology of PMPS is highly complicated and involves both peripheral and central sensitization. It results from injury to the peripheral nerves in the axilla or the chest wall during the dissection of axillary lymph nodes. Multiple risk factors are involved in the development of PMPS including acute postoperative pain, age \< 40 years, increased BMI , diagnosis at later-stage disease, psychosocial factors (i.e., anxiety, depression, sleep disturbances, catastrophizing), preoperative pain and adjuvant therapy (chemotherapy, radiation therapy).(8)Because PMP involves issues associated not only with pain management, but also with psychosocial disruption, the assessment of each of these domains should be addressed routinely so as to enable early detection and treatment.

Different pharmacological tools have been in use for either prevention or treatment of such refractory pain syndrome with variable efficacy.

Tianeptine is a unique antidepressant and anxiolytic medication that stimulates the uptake of serotonin (5-hydroxytryptamine; 5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in brain tissue . It acts as a full agonist at the mu-type opioid receptor (MOR) , the serotonin receptor ,dopamine (D2/3) receptors and glutamate receptors .It also reduces the hypothalamic-pituitary-adrenal response to stress, and thus prevents stress-related behavioral issues.

Pregabalin is a new synthetic molecule and a structural derivative of the inhibitory neurotransmitter γ-aminobutyric acid. It is an α2-δ (α2-δ) ligand that has analgesic, anticonvulsant, anxiolytic, and sleep-modulating activities. Pregabalin binds potently to the α2-δ subunit of calcium channels, resulting in a reduction in the release of several neurotransmitters, including glutamate, noradrenaline, serotonin, dopamine, and substance P , Pregabalin has also been found to be effective at reducing acute postoperative pain The efficacy of pregabalin in treating acute postsurgical pain has been demonstrated in numerous studies. A recent meta-analysis has suggested that pregabalin, at all doses and administration regimens, has opioid-sparing effects and reduces pain scores in the postsurgical setting, at the expense of increased sedation and visual disturbances; however, the efficacy of pregabalin in providing such in various surgical categories remains uncertain, and it is not known whether the risk: benefit ratio is greater for certain surgical categories The aim of this study is to assess the efficacy of the perioperative use of Pregabalin versus Tianeptine on the emergence of PMPS in female patients undergoing MRM for breast cancer.

Eligibility criteria: Inclusion Criteria:

1. Breast cancer female patients.
2. ASA class II and III.
3. Age ≥ 18 and ≤ 60 Years.
4. Body mass index (BMI): \> 20 kg/m2 and \< 35 kg/m2.
5. Type of surgery; elective breast cancer surgery (either modified radical mastectomy or conservative breast surgery) combined with axillary dissection.

Exclusion Criteria:

1. Patient refusal.
2. Age \<18 years or \>65 years.
3. BMI \<20 kg/m2 and \>35 kg/m2.
4. Known sensitivity or contraindication to drugs used in the study (Pregabalin , Tianeptine , NSAIDs, or morphine ).
5. History of psychiatric disorders or history of major depression.
6. History of chronic pain that necessitates morphine at a daily dose of 30 mg or more (or equivalent opioids).
7. history of gapabentenoids or antidepressant intake in the preceding three months.
8. Major medical conditions.
9. Pregnancy or lactation.

Primary outcomes:
measure: the percentage of patients who developed Post Mastectomy Pain Syndrome (PMPS)
timeFrame: 6 months
Secondary outcomes:
measure: Changes and stability in Mean Arterial Blood Pressure (MAP)
timeFrame: every 15 minutes during the surgery then at 1, 2, 4, 8, 12, 16, 20 and 24 hours postoperatively
measure: Changes and stability in Heart Rate (HR)
timeFrame: every 15 minutes during the surgery then at 1, 2, 4, 8, 12, 16, 20 and 24 hours postoperatively
measure: Total amount of fentanyl consumed intraoperative
timeFrame: Time of surgery
measure: 1st time opioids requested post-operative.
timeFrame: 24 hours after the surgery
measure: Total amount of morphine consumed postoperatively
timeFrame: 24 hours after the surgery
measure: The degree of postoperative sedation according to Ramsay scores.
timeFrame: 24 hours
measure: Postoperative nausea and vomiting (PONV).
timeFrame: 24 hours
measure: Severity of PMPS according to Grading system for neuropathic pain (GSNP)
timeFrame: 6 motnths
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: National Cancer Institute Cairo University
Study officials:
affiliation: National Cancer Institute Cairo University
name: Ayman Sharawy Abdel Rahman Aboul Nasr, MD
role: PRINCIPAL_INVESTIGATOR
References:
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