Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Swiss Multi-centre, Randomized, Placebo Controlled Trial of Pregabalin for Prevention of Persistent Pain in High Risk Patients Undergoing Breast Cancer Surgery (PREVENT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03216187
Recruitment Status : Recruiting
First Posted : July 13, 2017
Last Update Posted : October 27, 2021
Sponsor:
Collaborators:
University Hospital, Geneva
Centre Hospitalier Universitaire Vaudois
University Hospital Inselspital, Berne
Information provided by (Responsible Party):
Benno Rehberg-Klug, University Hospital, Geneva

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.

Condition or disease Intervention/treatment Phase
Persistent Postoperative Pain Drug: Pregabalin Drug: Placebos Phase 3

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.

Layout table for study information
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
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

Resource links provided by the National Library of Medicine

Drug Information available for: Pregabalin

Arm Intervention/treatment
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.
Drug: Pregabalin
pregabalin 150 mg capsules
Other Name: Pregabalin 150mg capsules

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.
Drug: Placebos
capsules identical to pregabalin but without active drug
Other Name: placebo capsules




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. retention rates of pregabalin treatment [ Time Frame: 30 days ]
  3. acute pain intensity and patient-reported pain outcome at 24h [ Time Frame: 24 hours ]
    PAIN-OUT questionnaire

  4. pain intensity at rest and movement, pain interference [ Time Frame: 3, 6, and 12 months ]
    Brief Pain Inventory, BPI

  5. neuropathic pain [ Time Frame: 3, 6, and 12 months ]
    incidence of neuropathic pain defined as a DN4-self-evaluation score ≥4

  6. patient-reported relevance of pain [ Time Frame: 3, 6, and 12 months ]
    response to the question: "do you consider your pain as significant?"

  7. 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?")

  8. 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?")



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Benno Rehberg-Klug, MD +4179 55 32132 benno.rehberg-klug@hcuge.ch
Contact: Stanislas Mathivon, MS +41795533678 stanislas.mathivon@hcuge.ch

Locations
Layout table for location information
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         
Sponsors and Collaborators
Benno Rehberg-Klug
University Hospital, Geneva
Centre Hospitalier Universitaire Vaudois
University Hospital Inselspital, Berne
Investigators
Layout table for investigator information
Study Director: Benno Rehberg-Klug, MD HUG
Study Director: Marc Suter, MD CHUV
Study Director: Ulrike Stamer, MD Inselspital
Layout table for additonal information
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: October 27, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
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