Traumeel is a broad-spectrum, anti-edematous, antiexudative, anti-inflammatory analgesic composed of biological and mineral substances, and it is a homeopathic combination medication. It has been used to treat inflammation and a variety of injuries, mainly to stimulate wound healing, provide pain relief, stop bleeding, improve muscle tone, and for a potential antiviral effect. It is a safe alternative to nonsteroidal anti-inflammatory medication.1 It has 12 biological ingredients and 2 mineral substances: Arnica montana, radix (mountain arnica), Calendula officinalis (calendula), Hamamelis virginiana (witch hazel), Millefolium (milfoil), Belladonna (deadly nightshade), Aconitum napellus (monkshood), Chamomilla (chamomile), Symphytum officinale (comfrey), Bellis perennis (daisy), Echinacea angustifolia (narrow-leafed coneflower), Echinacea purpurea (purple coneflower), Hypericum perforatum (St John's wort), Hepar sulphuris calcareum (calcium sulfide), and Mercurius solubilis (no common name).
The objectives of this study were to explore the nature of adverse events caused by Traumeel and to research its possible interaction with biological function and/or gastrointestinal tract occult bleeding. Our primary objective was to document any adverse reactions to the study medication, and the secondary objective was to document any significant variation in physiological parameters.
This study was designed to evaluate the clinical safety of Traumeel by instructing healthy subjects to ingest the medication on a daily basis. Adverse effects and physiological parameters were evaluated throughout the study. The Human Research Review Committee of the University of New Mexico School of Medicine approved this study on the basis of the final protocol in April 1998.
METHODS
Subject Population
Twenty healthy volunteers from the University of New Mexico Hospital who met the inclusion criteria were enrolled in the study. The volunteers received detailed written information on the trial medication and study procedures. In addition, the participants were informed about the possible risks of the study medication by a physician or nurse, and subjects provided written informed consent. The subjects were informed that they could withdraw from the study at any time by their own discretion. The confidentiality of any medical data collected in the study was maintained respective to applicable federal and state laws and regulations.
Healthy men and women aged 18 to 75 years were eligible to participate. Children, pregnant or lactating women, patients with known allergies to the study drug, and subjects taking any investigational drug within 4 weeks of the start of the study were excluded. Other exclusion criteria included inability to comply with the trial protocol, concomitant diseases, adverse events due to use of a birth control pill, and use of illegal substances. Subjects taking drugs or other therapies with comparable/interactive effects to the study drug or synthetic medications or herbal substances were asked to stop the regimens at least four weeks before participation in the study.
Medication
The study medication was first dispensed during the baseline visit. The subjects were instructed to take two Traumeeltablets (300 mg each) sublingually at 8:00 am, noon, and 5:00 pm every day, for a total of 28 days. A research coordinator reminded each subject to take the medication at the designated times. Subjects were instructed to take the medication at least 10 minutes before eating or drinking. The usual therapeutic dose is one tablet three times per day. The number of tablets given to the subject was compared with the remaining tablets to assess compliance. Each subject's daily log was inspected to evaluate compliance. No concomitant medications were allowed throughout the study except for birth control pills.
Assessments
The first visit to the study center was the baseline screening visit, during which each subject's medical history was taken, including history of cardiovascular; head, eyes, ears, nose, and throat; pulmonary; gastrointestinal; endocrine; musculoskeletal; neurologic; renal; hepatic; and psychiatric diseases. A history was also taken of allergic reactions, past alcohol and drug abuse, and current medications. A physical examination with vital signs was performed at baseline and posttreatment. A serum sample to determine prothrombin time (PT), partial thromboplastin time (PTT), complete blood cell count, liver and kidney profile, and clinical chemistry and a stool sample to test for occult blood were collected during this visit. A urine pregnancy test was also administered to all female subjects. At this first visit, informed consent was discussed and signed.
Participants were required to fast for eight hours prior to each visit after 7, 14, 21, and 28 days had passed for individual weekly follow-up. During the subsequent follow-up visits, serum and stool samples were collected to evaluate any physiological changes due to ingestion of the study medication. The following measurements were performed: blood pressure (systolic and diastolic), heart rate measurements in sitting position, respiratory frequency, oral body temperature. Laboratory analyses were performed at the University of New Mexico Hospital Laboratory, 2211 Lomas Boulevard NE, Albuquerque, NM 87131. Hemoglobin, hematocrit, red blood cells, white blood cells with differential count, neutrophils, and platelet counts were measured at baseline and each follow-up visit. Creatinine, fasting glucose, sodium, potassium, albumin, g-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin measures were also performed at baseline and each follow-up visit. Analyses of PT and PTT were performed at baseline, week 2, and the final visit.
Each subject's daily log was evaluated for occurrence of adverse events and study drug compliance. During the final visit, a physical examination recheck was performed on each subject. There were no dropouts or premature terminations of subject participation in the study.
Adverse Events
Adverse events included all disturbances of general health status, subjective and objective disease symptoms (including relevant changes of laboratory values), intercurrent diseases, observed in the context of the trial irrespective of a possible causal relationship with administration of the study drug. Each subject reported adverse events in the daily diary provided by the investigator. Interim analysis was made at 7, 14, and 21 days by examination of the patient diary.
Regardless of causal relationship, all adverse events reported by subjects or observed by the investigator were recorded on the Adverse Events Data Sheet. Severity of the adverse event was ranked on a scale from 1 to 4: 1=mild; 2=moderate; 3=severe; and 4=life-threatening. Relationship of each adverse event to the ingestion of the study drug was ranked on a scale from 1 to 5: 1=unrelated; 2=remote; 3=possible; 4=probable; and 5=related. Action taken to relieve the adverse event was categorized from 1 to 4: 1=no action taken; 2=discontinued drug; 3=treatment required; and 4=hospitalization required. Finally, the outcome of the adverse event was ranked as 1=event resolved or 2=event or reaction continues. Had any serious adverse events occurred they would have been reported immediately by the primary investigator to the Scientific Department of HEEL Inc., the manufacturer of the drug.
Statistical Analysis
The independent variable was treatment by the study drug taken over the course of 28 days. The dependent variables were the laboratory test variables, adverse events, severity of adverse events, relationship of adverse events to administration of the study drug, action taken to resolve the event, and outcome of the adverse events. The study conditions were standardized throughout the group. The sample size (n=20) was decided by the sponsor, Heel Inc., 11600 Cochiti Street SE, Albuquerque, NM 87123. The study was a within-subjects design and was not blinded.
All adverse events were listed together with information on onset, duration, severity, relationship to drug, and outcome. Frequency statistics were run to evaluate the frequency of adverse events, their severity, their relationship to study medication, any action taken to resolve them, and the outcomes of the events. A paired samples t test was used to evaluate changes that occurred in the physiological variables from baseline to posttreatment. The biometrical evaluation was performed using a personal computer with the SPSS statistical software package (SPSS Inc, Chicago, Ill.). The study conformed to the principles of the Declaration of Helsinki as well as with German drug law and the requirements thereof.
