E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
A recent Danish study published during spring 2013 advances a remarkable cause and treatment with Amoxicillin for a selected sub-group of low back pain patients.The study was based upon a hypothesis that chronic low back pain may arise from a low-grade infection of the intervertebral disc by the anaerobic Proprione acne bacteria, resulting in pain and bone edema (Modic changes). The main scope of this RCT is to re-examine the effect of amoxicillin in this patient group. |
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E.1.1.1 | Medical condition in easily understood language |
The sub-group of patients with chronic low back pain, earlier disc herniation, and focal vertebral bone marrow changes (Modic Changes) on magnetic resonance imaging (MRI). |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To re-examine the finding that antibiotic treatment can cure patients with chronic low back pain, earlier disc herniation, and Modic changes.
We will evaluate the effect of antibiotic treatment versus placebo on pain and disability, bothersomeness, health-related quality of life, sick leave, patients’ satisfaction and side effects from inclusion to 1-year follow-up. Our trial will be the first to re-examine the Danish Modic-antibiotica study.
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E.2.2 | Secondary objectives of the trial |
To compare change in Modic changes on MRI from inclusion to 1-year follow-up between treatment groups, and to assess whether characteristics of Modic changes by different MRI methods are related to the clinical effects of antibiotic treatment.
Further, to contribute to a clarification of the pathogenesis of Modic changes by studying gene expression of inflammatory biomarkers, and to conduct health economic analysis. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria will be as follows:
•Age between 18 and 65 years
•LBP of > 6 months duration in the area from L1 to L5 with a Numerical Rating Scale (NRS) score of 5 (mean of three NRS scales; current LBP, the worst LBP within the last 2 weeks, and usual/mean LBP within the last 2 weeks).
•MRI-confirmed disc herniation within the preceding 2 years or degenerated disc (Pfirrmann grade 348) at level L3/L4, L4/L5 or L5/S1.
•MC type I or type II adjacent to a previously herniated disc or adjacent to a degenerated disc (Pfirrmann grade 348), based on T1- and T2 weighted MRI.
•Both conservative and surgically treated patients will be included.
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E.4 | Principal exclusion criteria |
Exclusion criteria:
•Allergy to antibiotics or gradolinium contrast
•Current pregnancy or lactation
•Any kidney disease or pending litigation
•Any specific LBP diagnosis that may explain patients symptoms.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measures in the clinical part of the study will be pain and disability measured by the Norwegian version of the disease-specific Roland and Morris Questionnaire (RMQ)24;50. The RMQ ranges from 0 to 24, with lower score indicating less severe pain and disability. A clinically important change will be defined as a 30 % reduction of the individual’s baseline score. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Change in RMQ wil be evaluated at 1-year follow-up. |
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E.5.2 | Secondary end point(s) |
Secondary outcomes will be lumbar pain and leg pain, hours with pain during the last 4 weeks, bothersomeness, health-related quality of life (EuroQoL-5D), days with sick leave, patient’s satisfaction, and functional capacity (Oswestry Disability Index). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Data will be collected at baseline during follow-up, and at 1-year follow-up. Secondary outcomes will be evaluated at 1 year follow-up. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Radiological, genetics and health economics. |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 36 |
E.8.9.1 | In the Member State concerned days | |