Improving Pain Management and Long Term Outcomes Following High Energy Orthopedic Trauma (Pain Study)

NCT01789216 | Completed Phase 3 DMC

• 1 other identifier: W81XWH1020090
• Study Type: interventional
• Target: 450
• Locations: 1 country
• Sites: 17

Brief Summary

The purpose of this study is to definitively resolve questions regarding the use of multimodal pharmacologic pain management for orthopedic trauma patients in the context of a multicenter, randomized clinical trial. Also, as a significant proportion of this population develops chronic post traumatic osteoarthritis (PTOA), a sub-objective of this study is to examine the etiology and incidence of chronic pain and PTOA in this population.

Conditions

Orthopaedic Fractures

Keywords

Pilon fractures; Calcaneus fractures; Acute pain; Chronic pain; Isolated; unilateral; Grade I; Grade II; open; closed

Outcome Measures

Primary Outcomes (3)

• Opioid Utilization

  Morphine equivalent opioid utilization during initial hospitalization through 48 hours following definitive fixation.

  1 year

• Persistent Pain

  Patient reported persistent pain states at standard of care visits 3, 6 and 12 months following hospital discharge. Measured using the Brief Pain Inventory (BPI) and an additional battery of questions to assess neuropathic pain (painDETECT).

  1 year

• Surgery for non-union

  Defined as non-prophylactic surgery for nonunion performed between six months and a year following initial hospital discharge.

  1 year

Secondary Outcomes (11)

• Post Surgical Pain Intensity

  2 days

• Pre Surgical Pain Intensity

  2 days

• Length of Index Hospitalization

  1 year

• Adverse Effects and Complications

  2-3 weeks

• Functional Outcome

  1 year

Other Outcomes (1)

• PTOA sub-study assessment

  1-2 years

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Standard pain management + perioperative intravenous placebo \& oral placebo. Control group will receive an oral dose of placebo up to two hours prior to surgery and twice daily for up to 48 hours following any surgery, in addition to an intravenous dose of placebo up to two hours prior to surgery and every 6 hours for up to 48 hours following surgery. All study medications will be in addition to standard of care pain medication. \*Previous preoperative protocol was removed due to difficulty of medication adherence and limited importance of preoperative regimen to the intervention overall.

Drug: placebo

NSAID

ACTIVE COMPARATOR

Standard pain management + perioperative intravenous ketorolac \& oral placebo. The NSAID group will receive 30 mg of intravenous (IV) ketorolac (Ketorolac 30 mg/ml dose vial, NDC 00409-3795-01; manufacturer: Hospira) administered up to two hours prior to the procedure and every 6 hours for up to 48 hours following the procedure. In addition, as part of the perioperative protocol, patients will receive an oral dose of placebo up to two hours prior to the procedure and every 12 hours for up to 48 hours following the procedure. \*Previous preoperative protocol was removed due to difficulty of medication adherence and limited importance of preoperative regimen to the intervention overall.

Drug: NSAID

Gabapentinoid

ACTIVE COMPARATOR

Standard pain management + perioperative intravenous placebo \& oral pregabalin. The Pregabalin group will receive an oral bolus dose of 300 mg of pregabalin up to two hours prior to the procedure and a 75 mg dose every 12 hours for up to 48 hours following the procedure. In addition, as part of the perioperative protocol, patients will receive an IV dose of placebo up to two hours prior to the procedure and every 6 hours for up to 48 hours following the procedure. \*Previous preoperative protocol was removed due to difficulty of medication adherence and limited importance of preoperative regimen to the intervention overall.

Drug: Gabapentinoids

Interventions

NSAID DRUG

Also known as: Meloxicam/Mobic (NDC 68382-000-01; manufacturer: Zydus; encapsulated in size AA, empty capsule shells, backfilled with Avicel by Fisher Clinical Services (Bristol), LLC), Ketorolac/Toradol (NDC 00409-3795-01; manufacturer: Hospira)

NSAID

Gabapentinoids DRUG

Also known as: Pregablin/Lyrica (NDC 00071-1014-68; manufacturer: Pfizer; encapsulated in size, AA empty capsule shells, backfilled with Avicel by Fisher Clinical Services, (Bristol) LLC,; Lyrica, NDC 00071-1018-68; manufacturer: Pfizer; encapsulated, in size AA empty capsule shells, backfilled with Avicel by Fisher Clinical, Services (Bristol) LLC)

Gabapentinoid

placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with one of the following types of injuries:
• Unilateral, Grade I \&II open or closed pilon (distal tibial plafond), calcaneus, talus fractures and Lisfranc dislocations requiring operative treatment with fixation; or
• Unilateral, open (type I, II, or IIIA) ankle fractures with associated dislocation on presentation (OTA 44B3 or 44C) requiring operative treatment with fixation; or
• Unilateral, open or closed distal and proximal humerus (OTA 11A-C and OTA 13 A-C); or
• Open femoral shaft fracture (OTA 32 A-C; Gustilo Type I-IIIC) or open or closed supracondylar femur fractures (OTA 33 A-C); or
• Open or closed tibial plateau or shaft fractures (OTA 42 A-C or 43 A-C)
• Any combination of the above injuries which are surgically treated as a whole
• Patients who present to the admitting hospital acutely or clinic following an initial assessment in the Emergency Department, for care up to 10 days following initial injury.
• Patients 18-80 years old inclusive.
• Patients who are English or Spanish competent.
• Treating physicians agree that none of the study drugs are indicated for standard of care treatment for this patient.
• Patients able to be followed at the METRC facility for at least 12 months following injury.

You may not qualify if:

• Patients unable to provide informed consent.
• Patients with chronic pain being presently treated with opioid or gabapentinoid prescription or any other alternative therapy.
• Patients who are current IVDA
• Patients with bilateral or ipsilateral injuries requiring surgery
• Patients with other orthopedic or non-orthopedic injuries requiring operative intervention
• Patients with severe osteopenia.
• Patients who are skeletally immature (defined as less than 18 years of age or no radiographic evidence of epiphyseal closure).
• Patients who are expected to have a post-surgical stay less than 24 hours.
• Patients with a history of allergy to any drugs in the study.
• Patients unable to swallow oral medications or without adequately functioning GI tract.
• Patients with a history of gastrointestinal bleeds or gastric perforation.
• Patients with a history of stroke or heart attack.
• Patients currently receiving an aspirin or NSAID regimen (exception: low dose (81 mg) aspirin. See section 6.5) Patients with any bleeding disorders.
• Patients with severe renal failure. Patients with moderate renal failure may participate in the study at a modified dose. See Section 9.6.
• Patients undergoing daily treatment with systemic glucocorticoids before surgery.

Sponsors & Collaborators

• Major Extremity Trauma Research Consortium: lead

Study Sites (17)

University of Miami Ryder Trauma Center

Miami, Florida, United States

Location

St. Mary's Medical Center

West Palm Beach, Florida, United States

Location

Eskenazi Health

Indianapolis, Indiana, United States

Location

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Location

Louisiana State University Health Sciences Center

Shreveport, Louisiana, United States

Location

Johns Hopkins University

Baltimore, Maryland, United States

Location

University of Maryland, R Adams Cowley Shock Trauma Center

Baltimore, Maryland, United States

Location

Boston Medical Center

Boston, Massachusetts, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, United States

Location

Penn State University M.S. Hershey Medical Center

Hershey, Pennsylvania, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Location

UT Health: The University of Texas Health Science Center at Houston Medical School

Houston, Texas, United States

Location

Naval Medical Center Portsmouth

Portsmouth, Virginia, United States

Location

MeSH Terms

Conditions

Acute Pain; Chronic Pain; Lymphoma, Follicular

Interventions

Anti-Inflammatory Agents, Non-Steroidal; Meloxicam; Ketorolac; Ketorolac Tromethamine; Pregabalin

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Anti-Inflammatory Agents; Therapeutic Uses; Antirheumatic Agents; Thiazines; Sulfur Compounds; Organic Chemicals; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Renan Castillo, PhD

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

• Lawrence Marsh, MD

  University of Iowa Hospitals & Clinics

  PRINCIPAL INVESTIGATOR

• Katherine Frey, RN, MPH, MS

  Johns Hopkins Bloomberg School of Public Health

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2013
• First Posted: February 12, 2013
• Study Start: July 1, 2013
• Primary Completion: December 31, 2018
• Study Completion: December 31, 2018
• Last Updated: February 3, 2021

Record last verified: 2021-02

Locations

US (17)