Study of Intra-articular Injections vs Placebo in Patients With Pain From Osteoarthritis of the Knee

NCT ID: NCT01887678

Last Updated: 2018-04-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 287 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2014-01-31

Brief Summary

The aim of this study is to evaluate the effectiveness and safety of a combined Traumeel® / Zeel® injection against placebo (saline) in patients with moderate-to-severe pain associated with osteoarthritis of the knee.

Detailed Description

The primary objective is to demonstrate the superiority of Traumeel® and Zeel® co-administered intra-articular (IA) injections vs placebo IA injections on the change in knee pain in patients with moderate to severe knee pain associated with osteoarthritis.

The secondary objectives are to evaluate reduction of pain and stiffness and change in physical function.

Safety is evaluated by the incidence of treatment emergent adverse events during the treatment period and follow up period for all randomized patients.

Conditions

Osteoarthritis, Knee

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Traumeel® / Zeel® Injectable Solution

Injection volume is 4.2 mL for active study medication (2.0 mL Zeel plus 2.2 mL Traumeel in one intra articular (IA) injection) on treatment days 1, 8 and 15.

Group Type: EXPERIMENTAL

Traumeel® / Zeel® Injectable Solution

Intervention Type: DRUG

Injection volume is 4.2 mL for active study medication (2.0 mL Zeel plus 2.2 mL Traumeel in one IA injection) on treatment days 1, 8 and 15.

Placebo injectable solution

Injection volume of placebo is 4.2 mL as well (taken from the 10.0 mL vial by unblinded staff member, rest to be kept for drug accountability)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo is an injection of Saline

Interventions

Traumeel® / Zeel® Injectable Solution

Injection volume is 4.2 mL for active study medication (2.0 mL Zeel plus 2.2 mL Traumeel in one IA injection) on treatment days 1, 8 and 15.

Intervention Type: DRUG

Placebo

Placebo is an injection of Saline

Intervention Type: DRUG

Other Intervention Names

Traumeel; Zeel; Saline

Eligibility Criteria

Inclusion Criteria

1. Osteoarthritis (OA) of the knee by American College of Rheumatology criteria

2. Men or women between 45-80 years of age.

3. Have documented diagnosis of primary OA of the target knee based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment of the target knee confirmed by standard post-anterior weightbearing X-ray of the knee in full extension taken </= 6 months prior to Visit 1.

4. Currently taking an Nonsteroidal anti-inflammatory drug (NSAID), or acetaminophen on a regular basis (4-7 days/ week) over last 2 weeks prior to Visit 1 and has experienced amelioration of pain on these medications.

5. Must have a 50-foot walk test pain score of less than 40 mm on a 100 mm VAS in the target knee at screening

6. Pain in the non-target (contralateral) knee must not be greater than 30 mm on a 100 mm VAS on 50-foot walk test, and the target knee must be more symptomatic.

7. Willingness to stop all OA treatments.

8. Fully informed of the risks of entering the study and willing to provide written consent to enter the study.

9. Able to understand and be willing to comply with all study requirements, particularly the weekly injection regimen for administration of study drug.

10. Primary complaint is pain immediately following an unassisted 50-foot walk. They must show:

1. moderate to severe pain score in the target knee as demonstrated by 40 - 90 mm recorded on a 100 mm VAS, and

2. 20 mm increase in pain from their screening visit pain score (a "flare")

3. pain in the non-target (contralateral) knee must </= 30 mm on a 100 mm VAS

Exclusion Criteria

1. Known hypersensitivity or allergy to any of the components of Traumeel or Zeel

2. Known hypersensitivity or allergy to acetaminophen.

3. Has body mass index (BMI) >38 kg/m2.

4. Avoidance of, or aversion to, nonprescription medications.

5. Clinical symptoms of meniscal instability or significant valgus/ varus that requires corrective osteotomy

6. Any major injury or surgery to the target knee in the prior 12 months.

7. One or a combination of the following co-morbidities:

1. other inflammatory arthropathies, gout or pseudogout within previous 6 months

2. avascular necrosis

3. severe bone or joint deformity in target knee

4. osteonecrosis of either knee

5. fibromyalgia

6. pes anserine bursitis

7. lumbar radiculopathy with referred pain to either knee

8. neurogenic or vascular claudication

9. significant anterior knee pain due to diagnosed isolated patella-femoral syndrome in the target knee

10. target knee joint infection or skin disorder/infection to the area surrounding the knee within previous 6 months

11. current treatment or treatment of cancer within the previous 2 years (excluding basal cell or squamous cell carcinoma of the skin)

8. Participated in any experimental drug or device study within the prior one (1) month and/or IA injections six (6) months.

9. Referred pain from other joints

10. Significantly debilitating concurrent infection(s)

11. Significant ligamentous instability

12. Any prior viscosupplementation therapy (in target knee) within 6 months prior to Screening

13. Systemic or IA injection of corticosteroids in any joint within 3 months of enrollment

14. Therapy with oral hyaluronic acid products, and/or oral pharmaceutical products containing glucosamine and/or chondroitin sulphate and/or diacerein

15. Therapy with opioids within the last 90 days including intra-dermal delivery systems (patches)

16. Therapy with autologous stem cells

17. Therapy with coumarins such as warfarin, Coumadin; heparin and derivative substances including low molecular weight heparin, synthetic pentasaccharide inhibitors of factor Xa such as fondaparinux and idraparinux; direct factor Xa inhibitors such as rivaroxaban and apixaban; direct thrombin inhibitors such as hirudin, lepirudin, bivalirudin, argatroban and dabigatran.

18. Concomitant inflammatory or other rheumatologic, neurological or cardiovascular diseases which could affect the evaluation of knee pain

19. Ongoing litigation for workers compensation for musculoskeletal injuries or disorders

20. Use of alcohol of more than 4 drinks per day

21. Clinically important axial deviation (varus, valgus) greater than 15 degrees

22. Concomitant severe OA of the hip or other joints, which might interfere with the assessments required by the study

23. Painful knee conditions other than OA (e.g., Paget's disease)

24. Hemiparesis of lower limbs

25. Significant planned surgery to lower limbs, which might interfere with the patient's ability to comply with study requirements

26. Presence of serious gastrointestinal, renal, hepatic, pulmonary, cardiovascular, neurological disease that might interfere with the outcome of the study or the patient's ability to comply with study requirements

27. Presence of infections and/or skin diseases in the area of the injection site such as psoriasis

28. Females who are pregnant or breast-feeding or not using recognized effective contraceptive measures. Females of childbearing potential (including those less than one year post-menopausal) must agree to maintain reliable birth control throughout the study.

29. Clinically significant abnormal laboratory values.

30. Patients who are likely to be non-compliant or uncooperative during the study.

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biologische Heilmittel Heel GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nebojsa Skrepnik, MD

Role: PRINCIPAL_INVESTIGATOR

Tucson Orthopaedic Institute

Royal Anspach, MD

Role: PRINCIPAL_INVESTIGATOR

Clinical Research Advantage - Arizona II

Hans Barthel, MD

Role: PRINCIPAL_INVESTIGATOR

Hans Richard Barthel, M.D., Inc.

Shariar Cohen-Gadol, MD

Role: PRINCIPAL_INVESTIGATOR

Westlake Medical Research

David Bolshoun, MD

Role: PRINCIPAL_INVESTIGATOR

Radiant Research Inc. - Denver

Linda Murray, DO

Role: PRINCIPAL_INVESTIGATOR

Radiant Research Inc

Susan Hole, DO

Role: PRINCIPAL_INVESTIGATOR

Riverside Clinical Research

Agustin Latorre, MD

Role: PRINCIPAL_INVESTIGATOR

AppleMed Research, Inc.

Richard Radnovich, DO

Role: PRINCIPAL_INVESTIGATOR

Injury Care Medical Center

Moges Sisay, MD

Role: PRINCIPAL_INVESTIGATOR

Global Scientific Innovations

Larkin T Wadsworth, MD

Role: PRINCIPAL_INVESTIGATOR

Sundance Clinical Research, LLC

Kurian Abraham, MD

Role: PRINCIPAL_INVESTIGATOR

New Hope Clinical Research

Rakesh Patel, MD

Role: PRINCIPAL_INVESTIGATOR

PMG Research of Salisbury

George Raad, MD

Role: PRINCIPAL_INVESTIGATOR

PMG Research of Charlotte

Martin VanCleeff, MD

Role: PRINCIPAL_INVESTIGATOR

PMG Cary Medical Research

John Rubino, MD

Role: PRINCIPAL_INVESTIGATOR

PMG Research of Raleigh

Howard R Adelglass, MD

Role: PRINCIPAL_INVESTIGATOR

Research Across America - NY

Louis Re, MD

Role: PRINCIPAL_INVESTIGATOR

Manhattan Medical Research

Daniel Whitmer, MD

Role: PRINCIPAL_INVESTIGATOR

Clinical Inquest Center Ltd.

Jeffrey Klein, MD

Role: PRINCIPAL_INVESTIGATOR

Radiant Research Inc. - Akron

Rakesh Davit, MD

Role: PRINCIPAL_INVESTIGATOR

Sterling Research Group, Ltd.

Glenn Smith, DO

Role: PRINCIPAL_INVESTIGATOR

Hillcrest Clinical Research

Shawn Saylor, DO

Role: PRINCIPAL_INVESTIGATOR

Blair Orthopedic Associates, Inc

Alex Slandzicki, MD

Role: PRINCIPAL_INVESTIGATOR

Clinical Research Solutions

Sadia Dar, MD

Role: PRINCIPAL_INVESTIGATOR

Clinical Research Solutions

Rickey Manning, MD

Role: PRINCIPAL_INVESTIGATOR

PMG Research of Knoxville

Paul Wakefield, MD

Role: PRINCIPAL_INVESTIGATOR

PMG Research of Knoxville

Michael R Adams, MD

Role: PRINCIPAL_INVESTIGATOR

Radiant Research Inc. - Salt Lake City

Teresa Sligh, MD

Role: PRINCIPAL_INVESTIGATOR

Providence Clinical Research

David. Cardona, MD

Role: PRINCIPAL_INVESTIGATOR

Universal BioPharma Research Inc.

Locations

Clinical Research Advantage - Arizona II

Phoenix, Arizona, United States

Tucson Orthopaedic Institute

Tucson, Arizona, United States

Universal BioPharma Research Inc.

Dinuba, California, United States

Providence Clinical Research

North Hollywood, California, United States

Hans Richard Barthel, M.D., Inc.

Santa Barbara, California, United States

Westlake Medical Research

Westlake Village, California, United States

Radiant Research Inc. - Denver

Denver, Colorado, United States

Riverside Clinical Research

Edgewater, Florida, United States

AppleMed Research, Inc.

Miami, Florida, United States

Radiant Research Inc.

Pinellas Park, Florida, United States

Injury Care Medical Center

Boise, Idaho, United States

Global Scientific Innovations

Evansville, Indiana, United States

Sundance Clinical Research, LLC

St Louis, Missouri, United States

Manhattan Medical Research

New York, New York, United States

Research Across America - NY

New York, New York, United States

PMG Cary Medical Research

Cary, North Carolina, United States

New Hope Clinical Research

Charlotte, North Carolina, United States

PMG Research of Charlotte

Charlotte, North Carolina, United States

PMG Research of Raleigh

Raleigh, North Carolina, United States

PMG Research of Salisbury

Salisbury, North Carolina, United States

Radiant Research Inc. - Akron

Akron, Ohio, United States

Sterling Research Group, Ltd

Cincinnati, Ohio, United States

Clinical Inquest Center Ltd.

Dayton, Ohio, United States

Hillcrest Clinical Research

Oklahoma City, Oklahoma, United States

Blair Orthopedic Associates, Inc.

Altoona, Pennsylvania, United States

Clinical Research Solutions

Franklin, Tennessee, United States

PMG Research of Knoxville

Knoxville, Tennessee, United States

PMG Research of Knoxville

Knoxville, Tennessee, United States

Clinical Research Solutions

Smyrna, Tennessee, United States

Radiant Research Inc. - Salt Lake City

Salt Lake City, Utah, United States

Countries

United States

References

Lozada CJ, del Rio E, Reitberg DP, Smith RA, Kahn CB, Moskowitz RW. A double-blind, randomized, saline-controlled study of the efficacy and safety of co-administered intra-articular injections of Tr14 and Ze14 for treatment of painful osteoarthritis of the knee: The MOZArT trial. Eur J Integr Med 2017;13:54-63. DOI: 10.1016/j.eujim.2017.07.005;

Reference Type: RESULT

Other Identifiers

C1301

Identifier Type: -

Identifier Source: org_study_id