Diclofenac plus B vitamins versus diclofenac monotherapy in lumbago: the DOLOR study

Abstract

Objectives:

To assess the influence of vitamins B1, B6 and B12 on the analgesia success achieved by diclofenac in subjects with acute lumbago.

Research design and methods:

A randomised, double blind controlled clinical study in parallel groups, in which subjects received twice-daily oral administration of either the combination therapy, Group DB (50 mg diclofenac plus 50 mg thiamine, 50 mg pyridoxine and 1 mg cyanocobalamin) or diclofenac monotherapy, Group D (50mg diclofenac). The study period lasted a maximum of 7 days. If sufficient pain reduction was achieved (defined as Visual Analogue Scale <20 mm and patient's satisfaction), subjects could withdraw from the treatment after 3 or 5 days. All subjects gave written informed consent to participate in the study.

Main outcome measures:

The primary confirmatory study objective was to determine the number of patients with sufficient pain reduction after 3 days of treatment.

Results:

Three hundred and seventy-two subjects were allocated at random to either treatment group: Group DB – 187 subjects and Group D – 185 subjects. After 3 days of treatment, a statistically significant higher proportion of subjects in Group DB (n = 87; 46.5%) than in Group D (n = 55; 29%) terminated the study due to treatment success (χ²: 12.06; p = 0.0005). Furthermore, the combination therapy yielded superior results in pain reduction, improvement of mobility and functionality. Drug safety monitoring profile throughout the trial was within the expected safety profile of diclofenac.

Conclusions:

The combination of diclofenac with B vitamins was superior to diclofenac monotherapy in lumbago relief after 3 days of treatment. As a study drawback, daily VAS measurements were only recorded until subject withdrawal from treatment, whether after 3, 5, or 7 days. There were no differences in safety profile between the two study groups.

Key words: :

• Cyanocobalamin
• Diclofenac
• Low back pain
• Lumbago
• Pyridoxine hydrochloride
• Thiamine mononitrate

Transparency

Declaration of funding

This study was funded by a research grant from Centro Universitário Serra dos Órgáos – UNIFESO. Merck SA, Brazil (an affiliate of Merck KGaA) donated the drugs for this study. Aside from donation of the medications used in the clinical trial, there was no funding or any other form of financial contribution and/or support from Merck. The authors did not receive honoraria for performing the study or preparing the manuscript.

Declaration of financial/other interests

All the authors have disclosed that they have no relevant financial relationships.

Some peer reviewers receive honoraria for their review work in CMRO. Peer Reviewer 1 has disclosed that he/she is a scientific consultant on clinical trials to Jamieson Laboratories Inc. Peer Reviewer 2 has no relevant financial relationships.

Acknowledgements

The authors acknowledge the commitment and collaboration of the following individuals: Renato Kaufman, MD (Hospital de Cardiologia de Laranjeiras) for patient referral and physical examination; Prof. Oscar Roberto Guimarães (Centro Universitário Serra dos Órgãos – UNIFESO) for laboratory exam collection and analysis. Prof. Rafael Varella (Centro Universitário Serra dos Órgãos – UNIFESO; Universidade Federal do Rio de Janeiro - UFRJ) for data collection. Ernst M.W. Koch, PhD (Schmerzzentrum Frankfurt, Alsbach) for data revision and help with statistical analysis. Dieter Bonke, PhD (Merck KGaA) and Prof. Manfred Zimmermann (Neuroscience and Pain Research Institute, Heidelberg) for comments on the draft manuscript. João Gabriel Daher (Centro Universitário Serra dos Órgãos – UNIFESO), Mariana Thomé (Centro Universitário Serra dos Órgãos – UNIFESO), Marcelo Paula Coutinho MD (Universidade Federal do Rio de Janeiro – UFRJ) for study monitoring.