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

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.

Study Overview

• Status: Terminated
• Conditions: Persistent Postoperative Pain
• Intervention / Treatment: Drug: Pregabalin; Drug: Placebos

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.

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 3

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital
  • Bern, Switzerland
    • Brustzentrum Bern
  • Geneva, Switzerland, 1211
    • Hôpitaux Universitaires de Genève HUG
  • Geneva, Switzerland
    • Clinique des Grangettes
  • Genolier, Switzerland, 1272
    • Clinique de Genolier
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois CHUV

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: placebo capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of "clinically important pain" at 3 months after surgery	"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.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pregabalin-related side effects	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	10 days
retention rates of pregabalin treatment		30 days
acute pain intensity and patient-reported pain outcome at 24h	PAIN-OUT questionnaire	24 hours
pain intensity at rest and movement, pain interference	Brief Pain Inventory, BPI	3, 6, and 12 months
neuropathic pain	incidence of neuropathic pain defined as a DN4-self-evaluation score ≥4	3, 6, and 12 months
patient-reported relevance of pain	response to the question: "do you consider your pain as significant?"	3, 6, and 12 months
Patient-reported acceptance of the preventive treatment	response to the question "In retrospect, do you consider the preventive treatment worthwhile, given your pain outcome and your experience of taking the medication?")	3 months
Expectations about treatment benefits before treatment and after	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?")	10 days

Collaborators and Investigators

• Sponsor: Benno Rehberg-Klug
• Collaborators: University Hospital, Geneva; Centre Hospitalier Universitaire Vaudois; Insel Gruppe AG, University Hospital Bern
• Investigators: Study Director: Benno Rehberg-Klug, MD, HUG; Study Director: Marc Suter, MD, CHUV; Study Director: Ulrike Stamer, MD, Inselspital

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2018
• Primary Completion (Actual): June 11, 2024
• Study Completion (Actual): November 29, 2024

Study Registration Dates

• First Submitted: July 10, 2017
• First Submitted That Met QC Criteria: July 10, 2017
• First Posted (Actual): July 13, 2017

Study Record Updates

• Last Update Posted (Estimated): October 7, 2025
• Last Update Submitted That Met QC Criteria: October 1, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Amino Acids, Peptides, and Proteins; Organic Chemicals; Acids, Acyclic; Carboxylic Acids; Amino Acids; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Pregabalin
• Other Study ID Numbers: PREVENT (Janssen Biotech Inc.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No