PROTOCOL SUMMARY - School of Medicine Web viewMajor Extremity Trauma Research Consortium (METRC):...
Transcript of PROTOCOL SUMMARY - School of Medicine Web viewMajor Extremity Trauma Research Consortium (METRC):...
Major Extremity Trauma Research Consortium (METRC):
Improving Pain Management and Long Term Outcomes Following High Energy Orthopedic Trauma (Pain Study)
Financial Sponsor: DOD OETRP/CDMRP/NIH
Contract Number: W81XWH1020090
IND# N/A
IDE# N/A
Principal Investigators/Protocol Chairs:
Renan C. Castillo, PhD
Srinivasa N. Raja, MD
Principal Investigators PTOA Pilot Study:
J. Lawrence Marsh, MD
Don Anderson, PhD
Medical Monitor: Marc Swiontkowski, MD
Version # 11.0
DATE: October 20, 2015
This template is adapted from the ICH guidance document E6 (Good Clinical Practices), Section 6.
Confidentiality Statement
This document is confidential and is to be distributed for review only to investigators, potential investigators, consultants, study staff, and applicable independent ethics committees or institutional review boards. The contents of this document shall not be disclosed to others without written authorization from METRC (or others, as applicable), unless it is necessary to obtain informed consent from potential study participants.
Signature Page
The signature below constitutes the approval of this protocol and the attachments, and provides the necessary assurances that this trial will be conducted according to all stipulations of the protocol, including all statements regarding confidentiality, and according to local legal and regulatory requirements and applicable U.S. federal regulations and ICH guidelines.
The Lead Principal Investigator (Protocol Chair) should sign Signature Page 1. A copy of this Signature Page 1 should be filed with the holder of the Regulatory documents and a copy should be maintained at the site.
Principal Investigator: _______________________________________________
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Signed:
Date:
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Pain Protocol v 11.0 10/20/1580
CONTENTS
Signature PageiiPROTOCOL SUMMARY91. KEY ROLES172. BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE182.1 Background Information182.2 Rationale212.3 Potential Risks and Benefits223. STUDY OBJECTIVES243.1 Primary Objective243.2 Secondary Objectives244. STUDY DESIGN254.1 Description of the Study Design254.2 Study Endpoints275. STUDY POPULATION275.1 Description of the Study Population275.2 Strategies for Recruitment286. STUDY TREATMENTS296.1 Description of the Study Treatment Arms296.2 Study Agent Administration346.3 Concomitant Medications and Procedures346.4 Assessment of Participant Adherence with Study Agent(s)/Intervention(s)346.5 Precautionary and Prohibited Medications and Procedures347. STUDY PROCEDURES/EVALUATIONS347.1 Clinical Evaluation357.2 Laboratory Evaluations377.3 Assessment of Participant Compliance with Study378. STUDY SCHEDULE378.1 Screening378.2 Enrollment/Baseline388.3 Randomization388.4 Follow-up398.5 Final Study Visit398.6 Early Termination Visit N/A408.7 Pregnancy Visit408.8 Unscheduled Visits409. ASSESSMENT OF SAFETY409.1 Definitions409.2 Methods and Timing for Assessing, Recording, and Analyzing, Managing Safety Parameters419.3 Adverse Event Reporting Procedures429.4 Reporting Pregnancy449.5 Type and Duration of the Follow-up of Participants After Adverse Events459.6 Modifications of Study Agent(s)/Intervention(s) for a Participant459.7 Halting Rules for the Protocol459.8 Stopping Rules for an Individual Participant/Cohort459.9 Premature Withdrawal of a Participant469.10 Replacement of a Participant Who Discontinues Study Treatment N/A4610. CLINICAL MONITORING STRUCTURE4610.1 Site Monitoring Plan4610.2 Safety Monitoring Plan4611. STATISTICAL CONSIDERATIONS4711.1 Overview and Study Objectives4711.2 Sample Size Considerations4711.3 Randomization4811.4 Missing Data4811.5 Planned Interim Analysis4911.6 Analysis Plan4912. QUALITY CONTROL AND QUALITY ASSURANCE5013. ETHICS/PROTECTION OF HUMAN SUBJECTS5113.1 IRB/Ethics Committee5113.2 Informed Consent Process51All recruitment materials will be provided in both English and Spanish.5213.2.2 Assessing Capacity to Consent and Consenting a Proxy Respondent5213.3 Exclusion of Women, Minorities, and Children (Special Populations)5213.4 Participant Confidentiality5213.5 Study Discontinuation5314. DATA HANDLING AND RECORD KEEPING5314.1 Data Management Responsibilities5314.2 Data Capture Methods5414.3 Types of Data5414.4 Source Documents and Access to Source Data/Documents5414.5 Timing/Reports5414.6 Study Records Retention5414.7 Protocol Deviations5515. PUBLICATIONS POLICY5516. SCIENTIFIC REFERENCES5517. APPENDICES61APPENDIX A: STUDY CONTACT ROSTER61APPENDIX B: PROTOCOL COMMITTEE62APPENDIX C: DATA COLLECTION SCHEDULE63APPENDIX D: ADVERSE EVENT GRADING TABLE*65APPENDIX E: Common and Infrequent Adverse Events for Study Drugs75APPENDIX F: CONSENT TEMPLATE78APPENDIX G: CONSENT TEMPLATE PILOT STUDY85APPENDIX H: EVALUTION TO GIVE CONSENT91APPENDIX I: STUDY INSERT92APPENDIX J: PATIENT DAILY LOG94
List of General Abbreviations/Terminology
AE
Adverse Event/Adverse Experience
CFR
Code of Federal Regulations
CIB
Clinical Investigators Brochure
CONSORT
Consolidated Standards of Reporting Trials
CRF
Case Report Form
DSMB
Data and Safety Monitoring Board
DSMC
Data and Safety Monitoring Committee
FDA
Food and Drug Administration
FWA
Federal-Wide Assurance
GCP
Good Clinical Practice
HIPAA
Health Insurance Portability and Accountability Act
IB
Investigators Brochure
ICF
Informed Consent Form
ICH
International Conference on Harmonization
IDE
Investigational Device Exemption
IND
Investigational New Drug
IRB
Institutional Review Board
ISM
Independent Safety Monitor
MedDRA
Medical Dictionary for Regulatory Activities
MOP
Manual of Procedures
NDA
New Drug Application
OHRP
Office for Human Research Protections
OHSR
Office for Human Subjects Research
PHI
Protected Health Information
PI
Principal Investigator
PK
Pharmacokinetics
QA
Quality Assurance
QC
Quality Control
SAE
Serious Adverse Event/Serious Adverse Experience
SMC
Safety Monitoring Committee
SOP
Standard Operating Procedure
WHO
World Health Organization
List of METRC Abbreviations/Terminology
CDMRP Congressionally Directed Medical Research Program.
DODDepartment of Defense
DOD HRPODOD Human Research Subject Protection Office.
Master Consent FormTemplate consent form designed for study by the MCC
Master IRB applicationTemplate IRB application designed for study by the MCC
MCCMETRC Coordinating Center
MCC Study ManagerPrincipal site contact for Research Coordinators at sites
MTF Core Clinical SitesMilitary Treatment Facilities Core Clinical
OETRPOrthopaedic Extremity Trauma Research Program
SCCSatellite Clinical Sites
AISite Associate Investigators.
RCSite Research Coordinator
RSSite Research Staff
Study NumberProtocol identification number
Study Principal InvestigatorLead Investigator on a protocol
Study Protocol CommitteeProtocol development
SOPStandard Operating Procedures
REDCapResearch Electronic Data Capture System
USAMRMC United States Army Medical Research and Material Command
PROTOCOL SUMMARY
Title: Improving Pain Management and Long Term Outcomes Following High Energy Orthopedic Trauma
Financial Sponsor: DoD CDMRP / National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type of study: The proposed study is a three arm, double blinded, randomized, placebo controlled multicenter Phase III clinical trial.
Objective: The objective 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. We will test whether adjunctive analgesic therapy during the pre and peri-operative period, in addition to standard of care pain management, can improve overall pain control and pain related outcomes without increasing analgesic related side effects.
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.
Study Groups: Patients will be randomized into three treatment groups. The intervention will begin within 48 hours of admission and continue for no longer than two weeks or up to 48 hours after definitive fixation.
Group 1: standard pain management, plus up to two weeks of oral placebo, plus intravenous and oral placebo for up to 48 hours at each surgical procedure.
Group 2: standard pain management, plus up to two weeks of oral non-steroidal anti-inflammatory drugs (NSAIDs) (meloxicam), plus intravenous NSAIDs (ketorolac) and oral placebo for up to 48 hours at each surgical procedure.
Group 3: standard pain management, plus up to two weeks of oral pregabalin, plus intravenous placebo and oral pregabalin for up to 48 hours at each surgical procedure.
Specific Aim 1: Evaluate the effect of standard pain management (Group 1) vs. standard pain management plus pre and peri-operative NSAIDs (Group 2 meloxicam + ketorolac) in the treatment of s