nus.edu.sg

INTRODUCTION: Phase III randomised clinical trials provide the highest level of evidence to support the superior effectiveness of a new drug or therapy. The main practical problems encountered in the initiation, design, conduct and completion of both investigator-initiated and sponsor-initiated phase III clinical drug trials will be reviewed. METHODS: A Medline search of clinical drug trials conducted in Singapore as well as journal articles highlighting important methodological considerations and practical problems encountered in phase III clinical trials was performed. RESULTS: Several phase III randomised clinical trials have been conducted in Singapore which include the investigation of interventions that include tramadol, estradiol patch and colloidal bismuth subcitrate. The main problems encountered in phase III clinical drug trials include difficulties with recruitment of subjects for the study, proper filing of case report forms, special problems in children and the elderly, adequate compensation for adverse events and the adequate archival of documents of the completion of trials. In investigator-initiated trials, careful attention should be given to identifying a suitable study question, choice of study design, sample size calculations and data analysis. In sponsor-initiated trials, a good working relationship with the sponsor is essential and publication terms should be spelt from the onset of the trial. CONCLUSIONS: Well-planned clinical trials led by a team of competent investigators are essential for the conduct of rigorous sponsor-initiated and investigator-initiated clinical trials.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11126694&dopt=Abstract tramadol Ultram




G Chir. 2000 Oct;21(10):405-8.
[Laparoscopic surgery of varicocele. Role of total endovenous anesthesia in same-day discharge]

[Article in Italian]

Dona B, Cantele P, Pianalto S, Funes M, Gagliardi G, Cappi F.

Dipartimento di Farmacologia e Anestesiologia, Universita degli Studi di Padova.

The success of out-patients laparoscopic surgery depends on a careful selection of patients and the ability of anesthetic technique to ensure a rapid emergence from anesthesia, with a satisfactory control of postoperative pain and the absence of side effects. This study was undertaken to investigate the influence of a total intravenous anesthetic management on the recovery process after laparoscopic varicocelectomy. Fifty-three ASA 1 patients aged 12-41 yrs (mean 26.02) scheduled to undergo laparoscopic varicocelectomy as day surgery procedure were included in this study. Propofol was used as inductor agent and in variable-rate infusion (170-100 mcg/Kg/min) to maintain anesthesia supplemented with Fentanyl (FNT) before endotracheal intubation, incision surgery and if the patient manifested clinical signs of inadequate analgesia. Local anesthesia was infiltrated into the skin before incision. Tramadol 100 mg and Ketorolac 30 mg were administered before the end of surgery to delay the onset of the postoperative pain. Pain was evaluated using a self-rating visual analoque scale (VAS) ranging from 0 to 10 at 0-0.5 hrs postoperatively and every 2 hrs until discharge. At the same time nausea was clinically evaluated using a scale ranging from 0 to 3. Postoperative pain and nausea (PONV) treatment were standardized. Patients were discharged by Post-Anesthesia Discharge Scoring System (PADS). Mean operating time was 34.2 min and mean estubation time was 11.6 min. At time 0 all patients had VAS pain score < 3, on the same time 2 of patients was treated for mild PONV; mean time to first request for postoperative analgesia treatment in 89% of patients was more than 6 hrs, 5 patients required pain treatment before discharge in a mean time 216' +/- 156'. Using the PADS system, 64% of patients were discharged at 4 hrs and 89% at 6 hrs after surgery. One patient was admitted to hospital for an overnight stay for walking dizziness; another was readmitted for surgical complications. This results suggest that the proposed anesthetic management provided adequate pain control with minimun postoperative nausea and a good recovery rate. This permitted a short postoperative hospital stay without compromising in safety, efficacy, or patient satisfaction.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11126741&dopt=Abstract tramadol Ultram




Arch Pharm (Weinheim). 2000 Nov;333(11):381-6.
Synthesis and analgesic activity of some quinazoline analogs of anpirtoline.

Radl S, Hezky P, Proska J, Krejci I.

Research Institute of Pharmacy and Biochemistry, Kourimska 17, 13060 Prague, Czech Republic.

New condensed derivatives of anpirtoline, in which the pyridine ring is replaced with quinoline, quinazoline, 7-chloroquinoline, and 7-chloroquinazoline nuclei, have been synthesized. Their receptor binding profiles (5-HT1A, 5-HT1B) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. The analgesic activity of compounds 4e-4g, and 4l are at least comparable to that of clinically used drugs flupirtine and tramadol under the same conditions.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11129980&dopt=Abstract tramadol Ultram




Life Sci. 2000 Mar;66(17):1627-37.
The antinociceptive effect of tramadol on a model of neuropathic pain in rats.

Apaydin S, Uyar M, Karabay NU, Erhan E, Yegul I, Tuglular I.

Ege University, Center for Drug R&D and Pharmacokinetic Applications, Bornova Izmir, Turkey.

The antinociceptive activity of tramadol was investigated on the vocalization threshold to paw pressure in a rat model of unilateral mononeuropathy produced by loose ligatures around the common sciatic nerve. Despite the analgesic activity of tramadol was clearly established in motor and sensory responses of the nociceptive system in rats, the effect of this atypical opioid on experimental neuropathic pain models is not investigated. The intraperitoneally injected tramadol (2.5, 5 and 10 mg/kg) produced a potent and dose-dependent antinociceptive effect on both lesioned and non-lesioned hind paws. However, the analgesic effect on the lesioned paw was significantly more potent than the non-lesioned paw. This effect was partially antagonized by intraperitoneally administered naloxone (0.1 mg/kg) suggesting an additional non-opioid mechanism. Our results suggest that tramadol may be useful for the alleviation of some symptoms in peripheral neuropathic conditions

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11261592&dopt=Abstract tramadol Ultram

uibk.ac.at

BACKGROUND: The introduction of the laparoscopic approach to bariatric surgery has brought similar advantages as those seen in general surgery. There have been no trials assessing postoperative pain after laparoscopic adjustable silicone gastric banding (LASGB). We compared prospectively postoperative pain and outcome in LASGB and laparoscopic cholecystectomy (LC), to determine if morbidly obese patients can expect the same benefits from a laparoscopic approach in gastric banding as those which are known for LC in non-obese and obese patients. METHODS: In a prospectively collected database of 80 patients undergoing LASGB, information including a survey assessing the postoperative pain, the amount of analgetic drugs used, operative reports, laboratory data, and follow-up data was collected. This was compared to an equal number of patients undergoing LC. Postoperatively, all patients received standardized pain medication of 150 mg tramadol per day. Pain was assessed twice on postoperative days 1-3 using a patient questionnaire. RESULTS: Patient characteristics and duration of hospital stay were similar in the two groups. Although there was no significant difference in type and intensity of pain experienced by the patients in either group, the gastric banding patients reported less postoperative pain overall than those in the LC group. CONCLUSION: The analyzed data show that LASGB offers the same advantages as other laparoscopic operations, in that it induces less pain and enables the patient to return quickly to normal activity and work. The advantage over the compared LC group may be due to higher patient motivation, but was not statistically significant.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11355028&dopt=Abstract tramadol Ultram