Swiss Multi-centre, Randomized, Placebo Controlled Trial of Pregabalin for Prevention of Persistent Pain in High Risk Patients Undergoing Breast Cancer Surgery (PREVENT)
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| ClinicalTrials.gov Identifier: NCT03216187 |
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Recruitment Status :
Recruiting
First Posted : July 13, 2017
Last Update Posted : January 21, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Persistent Postoperative Pain | Drug: Pregabalin Drug: Placebos | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 300 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | double-blinded, randomized, placebo-controlled trial |
| Masking: | Quadruple (Participant, Care Provider, 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)). |
| Primary Purpose: | Prevention |
| Official Title: | Swiss Multi-centre, Randomized, Placebo Controlled Trial of Pregabalin for Prevention of Persistent Pain in High Risk Patients Undergoing Breast Cancer Surgery |
| Actual Study Start Date : | January 9, 2018 |
| Estimated Primary Completion Date : | January 1, 2023 |
| Estimated Study Completion Date : | January 1, 2024 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Pregabalin
Pregabalin 150 mg twice daily, starting from the evening before surgery, continuing with two times 150mg per day for 12 days, and ending with one 150mg capsule every evening for the final 3 days.
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Drug: Pregabalin
pregabalin 150 mg capsules
Other Name: Pregabalin 150mg capsules |
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Placebo Comparator: Placebo
Identical placebo capsules twice daily, starting from the evening before surgery, continuing with two capsules per day for 12 days, and ending with one capsule every evening for the final 3 days.
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Drug: Placebos
capsules identical to pregabalin but without active drug
Other Name: placebo capsules |
- incidence of "clinically important pain" at 3 months after surgery [ Time Frame: 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.
- Pregabalin-related side effects [ Time Frame: 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 [ Time Frame: 30 days ]
- acute pain intensity and patient-reported pain outcome at 24h [ Time Frame: 24 hours ]PAIN-OUT questionnaire
- pain intensity at rest and movement, pain interference [ Time Frame: 3, 6, and 12 months ]Brief Pain Inventory, BPI
- neuropathic pain [ Time Frame: 3, 6, and 12 months ]incidence of neuropathic pain defined as a DN4-self-evaluation score ≥4
- patient-reported relevance of pain [ Time Frame: 3, 6, and 12 months ]response to the question: "do you consider your pain as significant?"
- Patient-reported acceptance of the preventive treatment [ Time Frame: 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 [ Time Frame: 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?")
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03216187
| Contact: Benno Rehberg-Klug, MD | +4179 55 32132 | benno.rehberg-klug@hcuge.ch | |
| Contact: Stanislas Mathivon, MS | +41795533678 | stanislas.mathivon@hcuge.ch |
| Switzerland | |
| Inselspital | Recruiting |
| Bern, Switzerland, 3010 | |
| Contact: Ulrike Stamer, MD +41 31 632 99 95 ulrike.stamer@dkf.unibe.ch | |
| Principal Investigator: Ulrike Stamer, MD | |
| Brustzentrum Bern | Recruiting |
| Bern, Switzerland | |
| Contact: Patrizia Sager, MD | |
| Principal Investigator: Patrizia Sager, MD | |
| Hôpitaux Universitaires de Genève HUG | Recruiting |
| Geneva, Switzerland, 1211 | |
| Contact: Domitille Dereu, MD +41795532086 domitille.dereu@hcuge.ch | |
| Principal Investigator: Domitille Dereu, MD | |
| Sub-Investigator: Georges Savoldelli, MD | |
| Clinique des Grangettes | Recruiting |
| Geneva, Switzerland | |
| Contact: Delphine Bachmann | |
| Principal Investigator: Sindy Monnier, MD | |
| Clinique de Genolier | Recruiting |
| Genolier, Switzerland, 1272 | |
| Contact: Magdalena Kohlik, MD | |
| Principal Investigator: Magdalena Kohlik, MD | |
| Centre Hospitalier Universitaire Vaudois CHUV | Recruiting |
| Lausanne, Switzerland, 1011 | |
| Contact: Marc Suter, MD + 41 (0)79 556 3479 Marc.Suter@chuv.ch | |
| Sub-Investigator: Chantal Berna-Renella, MD | |
| Sub-Investigator: Moira Baeriswyl, MD | |
| Principal Investigator: Marc Suter, MD | |
| Study Director: | Benno Rehberg-Klug, MD | HUG | |
| Study Director: | Marc Suter, MD | CHUV | |
| Study Director: | Ulrike Stamer, MD | Inselspital |
| Responsible Party: | Benno Rehberg-Klug, médecin adjoint agrégé, University Hospital, Geneva |
| ClinicalTrials.gov Identifier: | NCT03216187 |
| Other Study ID Numbers: |
PREVENT |
| First Posted: | July 13, 2017 Key Record Dates |
| Last Update Posted: | January 21, 2022 |
| Last Verified: | January 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Pain, Postoperative Postoperative Complications Pathologic Processes Pain Neurologic Manifestations Pregabalin Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs |
Anticonvulsants Calcium Channel Blockers Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Calcium-Regulating Hormones and Agents Anti-Anxiety Agents Tranquilizing Agents Central Nervous System Depressants Psychotropic Drugs |