Clinical trial NCT03216187: Swiss Multi-centre, Randomized, Placebo Controlled Trial of Pregabalin for Prevention of Persistent Pain in High Risk Patients Undergoing Breast Cancer Surgery
Official title: Swiss Multi-centre, Randomized, Placebo Controlled Trial of Pregabalin for Prevention of Persistent Pain in High Risk Patients Undergoing Breast Cancer Surgery
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Persistent Postoperative Pain
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
Collaborators: name: University Hospital, Geneva
name: Centre Hospitalier Universitaire Vaudois
name: Insel Gruppe AG, University Hospital Bern
First posted: 2017-07-13
Enrollment: 126
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double-blinded, randomized, placebo-controlled trial
Primary purpose: PREVENTION

Brief summary: This study will test the benefits and risks of using pregabalin perioperatively to prevent persistent postoperative pain in patients at high risk (\>30%) of developing such pain after breast cancer surgery.

Detailed description: BACKGROUND Persistent postsurgical pain occurs in more than 30% of patients undergoing breast cancer surgery. Evidence that gabapentinoids such as pregabalin may reduce the incidence of persistent postsurgical pain is ambiguous, potentially because in previous trials prophylactic treatment was administered to every patient undergoing surgery. The patients at low risk of long term pain, were exposed to side effects without much benefit to expect.

AIM Validating or refuting the utility of pregabalin to prevent long term post-operative pain in patients at high risk of persistent pain after breast cancer surgery.

METHODS Randomized, double-blind, placebo-controlled trial of pregabalin (2\*150mg from the day before breast cancer surgery until 2 weeks after surgery) in patients at high risk of persistent pain (\>30%). High-risk patients are identified by a risk score derived from a previous observational study. The main outcome is the incidence of clinically important pain (necessitating analgesic treatment, or having an intensity of \>3 at rest or \>5 on movement) at 3 months after surgery. Secondary outcomes are: incidence of neuropathic pain, pain interference, and incidences at 6 and 12 months of follow-up. In addition, side effects of pregabalin and the retention rate during the treatment period will be monitored, as well as patient expectancies.

RELEVANCE This is the first study for prevention of persistent postoperative pain which targets only high-risk patients, thus lowering a false negative outcome and averting the risk of side effects for patients at low risk.

The study is powered to show a reduction of the incidence of clinically important pain at 3 months of 20%. In the case the study shows that this can be achieved and pregabalin is well tolerated, the preventive use of pregabalin for breast cancer surgery would be justified at least in high-risk patients. On the other hand, a negative result would indicate the futility of pregabalin prevention, which is already in routine use in many hospitals.

Eligibility criteria: Inclusion Criteria:

* patients scheduled for breast surgery for cancer, either breast-conserving (tumorectomy/ quadrantectomy) or mastectomy, with or without immediate reconstruction, and with or without axillary dissection.
* patients of 18 years or more scheduled for above mentioned type of surgery
* ability to speak and read French, English or German
* high (\>30%) risk of clinically important persistent pain: identified with 2 or more points of a risk score including the items: pre-existing pain at surgical site (2 points), history of depression (1 point), age \< 50 years (1 point), and high expected acute pain (\>6/10, 1 point).
* Informed Consent as documented by signature.

Exclusion Criteria:

* Inability to understand the consent form and to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
* Participation in another study with investigational drug within the 30 days preceding and during the present study,
* Previous enrolment into the current study,
* Enrolment of the investigator, his/her family members, employees and other dependent persons
* Pregnancy or lactation - Renal insufficiency (creatinine clearance \< 60 ml/min)
* Allergy to pregabalin or the ingredients of the capsules
* Long-term preoperative therapy with gabapentinoids or high-dose opioids (more than 60 mg of morphine equivalents)
* Symptomatic cardiac insufficiency (peripheral oedema, NYHA class III - marked limitation of physical activity)
* Suicidal ideation, identified by the question: "have you been bothered by thoughts that you would be better off dead, or of killing yourself?"
* Planned fertility preservation immediately after surgery before a planned chemotherapy
* Known or suspected non-compliance, or substance-use disorder with impact on medication adherence

Primary outcomes:
measure: incidence of "clinically important pain" at 3 months after surgery
timeFrame: 3 months
Secondary outcomes:
measure: Pregabalin-related side effects
timeFrame: 10 days
measure: retention rates of pregabalin treatment
timeFrame: 30 days
measure: acute pain intensity and patient-reported pain outcome at 24h
timeFrame: 24 hours
measure: pain intensity at rest and movement, pain interference
timeFrame: 3, 6, and 12 months
measure: neuropathic pain
timeFrame: 3, 6, and 12 months
measure: patient-reported relevance of pain
timeFrame: 3, 6, and 12 months
measure: Patient-reported acceptance of the preventive treatment
timeFrame: 3 months
measure: Expectations about treatment benefits before treatment and after
timeFrame: 10 days
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Inselspital
city: Bern
country: Switzerland
facility: Brustzentrum Bern
city: Geneva
country: Switzerland
facility: Hôpitaux Universitaires de Genève HUG
city: Geneva
country: Switzerland
facility: Clinique des Grangettes
city: Genolier
country: Switzerland
facility: Clinique de Genolier
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois CHUV
Study officials:
affiliation: HUG
name: Benno Rehberg-Klug, MD
role: STUDY_DIRECTOR
affiliation: CHUV
name: Marc Suter, MD
role: STUDY_DIRECTOR
affiliation: Inselspital
name: Ulrike Stamer, MD
role: STUDY_DIRECTOR
References: