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

Persistent Postoperative Pain Clinical Trial

— PREVENT  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03216187
• Other study ID #: PREVENT
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 9, 2018
• Est. completion date: November 29, 2024

Study information

• Verified date: June 2024
• Source: University Hospital, Geneva
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 126
• Est. completion date: November 29, 2024
• Est. primary completion date: June 11, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pain, Postoperative
• Persistent Postoperative Pain

Intervention

Drug:
• Pregabalin
pregabalin 150 mg capsules
• Placebos
capsules identical to pregabalin but without active drug

Locations

Country	Name	City	State
Switzerland	Brustzentrum Bern	Bern
Switzerland	Inselspital	Bern
Switzerland	Clinique des Grangettes	Geneva
Switzerland	Hôpitaux Universitaires de Genève HUG	Geneva
Switzerland	Clinique de Genolier	Genolier
Switzerland	Centre Hospitalier Universitaire Vaudois CHUV	Lausanne

Sponsors (4)

Lead Sponsor	Collaborator
Benno Rehberg-Klug	Centre Hospitalier Universitaire Vaudois, Insel Gruppe AG, University Hospital Bern, University Hospital, Geneva

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	retention rates of pregabalin treatment		30 days
Secondary	acute pain intensity and patient-reported pain outcome at 24h	PAIN-OUT questionnaire	24 hours
Secondary	pain intensity at rest and movement, pain interference	Brief Pain Inventory, BPI	3, 6, and 12 months
Secondary	neuropathic pain	incidence of neuropathic pain defined as a DN4-self-evaluation score =4	3, 6, and 12 months
Secondary	patient-reported relevance of pain	response to the question: "do you consider your pain as significant?"	3, 6, and 12 months
Secondary	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
Secondary	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