Randomized Study of Pregabalin for Pain Reduction in Patients With Rest Pain and Lower Limb Ischemia

Condition(s) targeted: Critical Limb Ischemia; Arterial Occlusive Disease; Pain; Ischemia

Intervention: pregabalin (Drug); placebo (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Karolinska Institutet

Official(s) and/or principal investigator(s):
Eric Wahlberg, MD. PhD, Principal Investigator, Affiliation: Karolinska Institutet

Overall contact:
Eric Wahlberg, MD, PhD, Phone: +46 8 517 70000, Ext: 2239, Email: eric.wahlberg@ki.se

The hypothesis behind the trial is the concept that Pregabalin is effective in reducing pain at rest in lower limb ischemia, and the study evaluates active treatment or placebo added to the regular pain regimens for these patients.

Official title: Pregabalin for Pain Reduction in Critical Limb Ischemia - A Double Blind, Randomized Controlled Study

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Reduction in Rating Scale (RS) pain compared to baseline. RS Pain will be assessed at 7, 14 days for all participants and after 28 and 56 days for patients continuing the extended phase of study.

Secondary outcome:

Improvement in the Short Form 36 (SF-36) parameter "bodily pain".

The amount, dose and duration of concomitant pain medication use during study compared to use before study.

Safety outcomes and adverse events will be examined and recorded throughout the study. Patient reported dizziness will be recorded separately in the CRF, as well as blood pressure at visits.

Detailed description: Critical limb ischemia (CLI) is the end stage of peripheral arterial disease in the legs and is a consequence of deteriorating blood flow supply to the lower limbs. The clinical definition of CLI includes peripheral arterial disease and recurrent rest pain for at least two weeks with or without ulcers or gangrene.

In patients not amenable to revascularization - around 35% - amputation or palliative

conservative care remains the options. Pain control is a vital part of any treatment of these patients. Besides being the principal conservative treatment, also patients undergoing revascularization experience severe pain both during work up and after surgery.

Experimental data indicate that pain in CLI is multimodal and to a large extent neuropathic. Still, current therapy is mostly based on opioid treatment, which clinically often affects pain moderately. The doses required to influence pain are also associated to severe side effects. Accordingly, there is a great need to improve pain control in the rather common disease CLI.

comparisons: pregabalin up to 600mg daily in addition to regular pain regimens compared to placebo and regular pain regimens.

Minimum age: N/A. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Rest pain, gangrene or ulcers located below the patella for a duration of at least

two weeks (either one of these criteria are sufficient).

- One measurement of: Ankle blood pressure(ABP) <70 mm Hg, an toe blood pressure(TBP)

<50, or a TcPO2<45 mm Hg, or an ankle/brachial pressure index <0. 7 (either one of these criteria are sufficient).

- Informed consent obtained

Exclusion Criteria:

- Age < 55 years

- Women of childbearing potential

- Patients already medicating with Pregabalin or Gabapentin

- Creatinine clearance <30ml/min

- Amputation necessary within two weeks

- Revascularization necessary within two weeks (open vascular surgery or endovascular)

- A medical history of clear dizziness

- NYHA class IV heart failure

- Known hypotension, or having a systolic arm blood pressure <120 mm Hg (two

consecutive measurements with the patient lying supine)

- Simultaneous or previous (within 30 days prior to study entry participation in a

clinical study using experimental drugs or devices

- Mental condition making the subject unable to understand the concepts and risk of the

study

- Known allergies against pregabalin

Eric Wahlberg, MD, PhD, Phone: +46 8 517 70000, Ext: 2239, Email: eric.wahlberg@ki.se

Deptartment of Vascular Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Recruiting
Urban Vingren, MD, PhD
Urban Vingren, MD, PhD, Principal Investigator

Department of Vascular Surgery, Karolinska University Hospital, Stockholm SE-171 76, Sweden; Recruiting
Jonas Malmstedt, MD, Phone: +46 8 517 70000, Ext: 6895, Email: jonas.malmstedt@karolinska.se
Jonas Malmstedt, MD, Principal Investigator
Ulrika Palmer-Kazen, MD, PhD, Sub-Investigator

Deptartment of Surgery, South Hospital, Stockholm, Sweden; Not yet recruiting
Peter Konrad, MD, PhD
Peter Konrad, MD, PhD, Principal Investigator

Related publications:

Caraceni A, Zecca E, Bonezzi C, Arcuri E, Yaya Tur R, Maltoni M, Visentin M, Gorni G, Martini C, Tirelli W, Barbieri M, De Conno F. Gabapentin for neuropathic cancer pain: a randomized controlled trial from the Gabapentin Cancer Pain Study Group. J Clin Oncol. 2004 Jul 15;22(14):2909-17.

Hultgren R, Olofsson P, Wahlberg E. Sex-related differences in outcome after vascular interventions for lower limb ischemia. J Vasc Surg. 2002 Mar;35(3):510-6.

Starting date: June 2006
Last updated: January 28, 2009