Persistent Postoperative Pain
Conditions
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.
Interventions
DRUGPregabalin
pregabalin 150 mg capsules
DRUGPlacebos
capsules identical to pregabalin but without active drug
Sponsors
Benno Rehberg-Klug
University Hospital, Geneva
Centre Hospitalier Universitaire Vaudois
Insel Gruppe AG, University Hospital Bern
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
study drugs (including identical placebos) and randomisation lists are prepared by the hospital pharmacy and are kept secret from the investigators until the end of the study and the "freezing" of the electronic data base (an interim analysis will be performed when data for the primary outcome are available for 60 patients per arm. Stopping rules are a difference in the incidence of the primary outcome of less than 8.2% (futility) or more than 19.9% (superiority)).
Intervention model description
double-blinded, randomized, placebo-controlled trial
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| incidence of "clinically important pain" at 3 months after surgery | 3 months | "Clinically important pain" is defined by: taking analgesics for pain at the surgical site OR average resting pain at the surgical site \>3/10 OR average movement-induced pain at the surgical site \>5/10. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pregabalin-related side effects | 10 days | blurred vision or diplopia, somnolence or sleepiness, abnormal thinking, confusional state, disturbed attention, and falls, as well as the effects noted in the "generic assessment of side effects" GASE questionnaire |
| retention rates of pregabalin treatment | 30 days | — |
| acute pain intensity and patient-reported pain outcome at 24h | 24 hours | PAIN-OUT questionnaire |
| pain intensity at rest and movement, pain interference | 3, 6, and 12 months | Brief Pain Inventory, BPI |
| neuropathic pain | 3, 6, and 12 months | incidence of neuropathic pain defined as a DN4-self-evaluation score ≥4 |
| patient-reported relevance of pain | 3, 6, and 12 months | response to the question: "do you consider your pain as significant?" |
| Patient-reported acceptance of the preventive treatment | 3 months | response to the question "In retrospect, do you consider the preventive treatment worthwhile, given your pain outcome and your experience of taking the medication?") |
| Expectations about treatment benefits before treatment and after | 10 days | responses to the questions: "How much pain do you expect 3 months from now?"" "How efficient do you think the study treatment is against the long-term pain (i.e. what is the success rate in %)?" "How well do you think it will work for you? (i.e. reduction in pain score 0-10)". Beliefs about treatment attribution after 10 days of treatment (question: "Do you think that you received the real drug or the placebo?") |
Countries
Switzerland
Contacts
STUDY_DIRECTORBenno Rehberg-Klug, MD
HUG
STUDY_DIRECTORMarc Suter, MD
CHUV
STUDY_DIRECTORUlrike Stamer, MD
Inselspital
Outcome results
None listed