Tramadol Versus Placebo in the Management of Postoperative Pain Following Bunionectomy

• ClinicalTrials.gov Identifier: NCT03290378
• Recruitment Status: Completed
• First Posted: September 21, 2017
• Results First Posted: March 19, 2020
• Last Update Posted: March 19, 2020
• Sponsor: Avenue Therapeutics, Inc.
• Information provided by (Responsible Party): Avenue Therapeutics, Inc.

Study Description

Brief Summary:

The study evaluates the effectiveness and safety of IV tramadol compared to placebo managing postoperative pain following a bunionectomy

Condition or disease	Intervention/treatment	Phase
Pain Management	Drug: Tramadol; Other: Placebo	Phase 3

Detailed Description:

(Non-clinical summary)

Tramadol is a centrally-acting synthetic analgesic of the aminocyclohexanol group with opioidlike effects. Tramadol is extensively metabolized following administration, which results in a number of enantiomeric metabolites that display different opioid-receptor binding properties, and monoaminergic reuptake inhibition.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 409 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Randomized, Double Blind, Three-Arm Study to Evaluate the Efficacy and Safety of Tramadol Infusion (AVE-901) Versus Placebo in the Management of Postoperative Pain Following Bunionectomy
• Actual Study Start Date: September 19, 2017
• Actual Primary Completion Date: April 11, 2018
• Actual Study Completion Date: April 23, 2018

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: AVE-901 50 mg	Drug: Tramadol; IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44
Active Comparator: AVE-901 25 mg	Drug: Tramadol; IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44
Placebo Comparator: Placebo	Other: Placebo; IV; Placebo, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44

Outcome Measures

Primary Outcome Measures :

1. The Sum of Pain Intensity Differences (SPID) Through 48 Hours Post First Dose [ Time Frame: 48 hours post first dose ]
   Pain intensity was recorded using the Numerical Pain Rating Scale (NPRS) from 0 to 10, where 0 was no pain and 10 was the worst pain imaginable at hrs: .5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48. As higher pain scores indicate worse pain, a negative Pain Intensity Difference (PID) indicates less pain (improvement from baseline). Thus, SPID scores are expected to be negative if a patient's pain decreases over time, with the lower SPID values indicating greater reduction in pain intensity.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• The patient is male or female 18-75 years of age undergoing unilateral first metatarsal bunionectomy surgery
• Willing to give consent and able to understand the study procedures
• Female patients must be of non-childbearing potential or be practicing a highly effective contraception
• The patient must be willing to be housed in a healthcare facility and able to receive parenteral analgesia for at least 72 hours after surgery.
• The patient meets definition of American Society of Anesthesiologists (ASA) Physical Class 1, or 2.

Exclusion Criteria:

• Patient is not expected to receive a continuous infusion nerve block as described in the Post-Op anesthetic procedures protocol
• Patient is undergoing bilateral or revision bunionectomy surgery
• The patient has allergy or hypersensitivity (or is intolerant) to opioids or tramadol The patient has known physical dependence on opioids
• The patient has taken other prior/concurrent chronic medications that have not been at a stable dose for at least 2 weeks prior to screening
• The patient is taking herbal or dietary supplements or medications that are moderate or strong inhibitors of CYP2D6 or CYP3A4 or inducers of CYP3A4
• The patient has taken monoamine oxidase (MAO) inhibitors, trazodone, or cyclobenzaprine within 14 days prior to surgery
• The patient cannot be withdrawn from medications (at least 7 days prior to surgery) that may lower the seizure threshold (e.g. anti-psychotic agents, MAOI inhibitors) or which increase serotonergic tone (e.g. selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, triptans).
• The patient has a history of epilepsy, or is known to be susceptible to seizures
• The patient has a history of Long QT Syndrome or a relative with this condition
• The patient has expressed suicidal ideation or is considered to be at risk of suicide.
• The patient is morbidly obese (body mass index [BMI] ≥ 40 kg/m2) or has documented sleep apnea requiring pharmacological or device intervention.
• Clinically significant abnormalities in the judgement of the Investigator
• The patient was administered an investigational product within 30 days prior to Screening.
• The patient has previously participated in a clinical study with AVE-901.

Contacts and Locations

Locations

United States, California

Trovare Clinical Research

Bakersfield, California, United States, 93301

Lotus Clinical Research

Pasadena, California, United States, 91105

United States, Maryland

Cheseapeake Research Group, LLC

Pasadena, Maryland, United States, 21122

United States, Texas

H.D. Research Corporation

Houston, Texas, United States, 77004

Endeavor Clinical Trials, PA

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Avenue Therapeutics, Inc.

  Study Documents (Full-Text)

Documents provided by Avenue Therapeutics, Inc.:

Study Protocol and Statistical Analysis Plan  [PDF] October 24, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Singla NK, Pollak R, Gottlieb I, Leiman D, Minkowitz H, Zimmerman J, Harnett M, Ryan M, Lu L, Reines S. Efficacy and Safety of Intravenously Administered Tramadol in Patients with Moderate to Severe Pain Following Bunionectomy: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study. Pain Ther. 2020 Dec;9(2):545-562. doi: 10.1007/s40122-020-00184-2. Epub 2020 Jul 18.

• Responsible Party: Avenue Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03290378
• Other Study ID Numbers: AVE-901-102
• First Posted: September 21, 2017
• Results First Posted: March 19, 2020
• Last Update Posted: March 19, 2020
• Last Verified: September 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pain; Neurologic Manifestations; Tramadol; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents