E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The Randomized Clinical Trial (RCT) aims to prove the hypothesis that Intradiscal Methylene blue Injection is capable of better pain reduction than the best available treatment in patients suffering from axial low back pain of discogenic origin |
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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 |
The Randomized Clinical Trial (RCT) aims to prove the hypothesis that Intradiscal Methylene blue Injection is capable of better pain reduction than the best available treatment in patients suffering from axial low back pain of discogenic origin |
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E.2.2 | Secondary objectives of the trial |
Secondary objective will be to prove that the treatment improves function and quality of life.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Axial low back pain of presumed discogenic origin of at least 6 months duration and non responsive to treatment of at least 6 months conservative medical management. History consistent with discogenic low back pain ( e.g. predominant axial pain produced on lumbar motion, significant functional limitation in sitting duration and tolerance) A neurological exam without marked motor deficit. Age between18 and 65 years and painintensity should be NRS 5 or higher. In discography Todd Wetzel classification grade 2 and 3 and a provoked pain of at least NRS 5 |
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E.4 | Principal exclusion criteria |
Severe disc degeneration at the affected level as evidenced by >50% disc height loss on plain anteroposterior and lateral lumbar radiographs or CT/MRI. - Extruded or sequestered herniated nucleus pulposus at the affected level(s). - Body Mass Index BMI of ≥ 35 - Weighted pain with NRS below 5 - Previous lumbar back surgery ( e.g. Laminectomy, discectomy or fusion) - Invasive intradiscal procedure previously performed at the same level. - Moderate to severe spinal stenosis due to osteophyte and/or ligamentous overgrowth as evidenced by MRI or CT, provided stenosis is the cause of pain. - Moderate to severe endplate degenerative changes at the affected levels - Grate 1-2 spondylolisthesis - Pregnancy - Coagulopathy or oral anti-coagulant therapy - Infection - Patients incapable of following verbal or written instructions or with psychiatric problems potentially interfering with cooperation in the study - Discography: Appendix 1. - That shows a posterior annular disruption to extend into the outer annulus or beyond the confines of the outer annulus. - Discography without pain reproduction at the affected level( s), or with discordant pain at adjacent unaffected levels at up to 50 Psi above opening pressure. - Pain provocation in disc at pressures >50 Psi above opening pressure - Todd Wetzel classification grade 1, 4 and 5. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary study parameter is pain at 6 months measured by the NRS according to Jensen (mean pain NRS; measured three times a day for 4 days,) NRS pain highest and lowest for back pain and the Patients Global Perceived Effect (GPE) measured by a 7 point Likert Scale. These parameters are registered at the standardized follow-up moments (6 weeks, 3, 6, and 12 months). Additional main study parameter of the Case series and RCT is also complications and side effects. Number of adverse and serious adverse events such as nerve damage or discitis. (Note: Both are theoretical possible but have not been reported until date) |
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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 | Yes |
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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
caseseries followed by a RCT |
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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.8.3 |
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 | 2 |
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 | Information not present in EudraCT |
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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A positive outcome of the case series, sufficient to start the RCT, is defined as a pain decrease of at least 2.5 NRS points in minimally 40% of the treated patients and this without noteworthy side-effects or complications. The case series ends 6 months after inclusion of the last patient.
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |