Rationale and design of the RE-LATED AF--AFNET 7 trial: REsolution of Left atrial-Appendage Thrombus--Effects of Dabigatran in patients with Atrial Fibrillation.

Background: Dabigatran etexilate, a direct thrombin inhibitor and non-vitamin K antagonist oral anticoagulant (NOAC), has been shown to effectively prevent thromboembolic events in patients with non-valvular atrial fibrillation (AF). However, there is a paucity of data on the antithrombotic efficacy and safety of dabigatran in the resolution of left atrial appendage (LAA) thrombi in AF patients.

Objective: The primary objective of the RE-LATED AF trial is to assess whether dabigatran results in a faster complete LAA thrombus resolution as compared to vitamin K antagonist phenprocoumon.

Randomized controlled trials: part 17 of a series on evaluation of scientific publications.

Background: In clinical research, randomized controlled trials (RCTs) are the best way to study the safety and efficacy of new treatments. RCTs are used to answer patient-related questions and are required by governmental regulatory bodies as the basis for approval decisions.

Methods: To help readers understand and evaluate RCTs, we discuss the methods and qualitative requirements of RCTs with reference to the literature and an illustrative case study.

Rationale and design of the randomised clinical trial comparing early medication change (EMC) strategy with treatment as usual (TAU) in patients with major depressive disorder--the EMC trial.

Background: In major depressive disorder (MDD), the traditional belief of a delayed onset of antidepressants' effects has lead to the concept of current guidelines that treatment durations should be between 3-8 weeks before medication change in case of insufficient outcome. Post hoc analyses of clinical trials, however, have shown that improvement usually occurs within the first 10-14 days of treatment and that such early improvement (Hamilton Depression Rating Scale [HAMD] decrease >or=20%) has a substantial predictive value for final treatment outcome. Even more important, non-improvement (HAMD decrease <20%) after 14 days of treatment was found to be highly predictive for a poor final treatment outcome.

Surgical management of subfoveal choroidal neovascular membranes in age-related macular degeneration by macular relocation: experiences of an early-stopped randomised clinical trial (MARAN Study).

Rationale: The MARAN (Macular Relocation in Age-related Neovascular disease) trial was planned to assess the effectiveness of full macular relocation (MR) in patients with neovascular age-related macular degeneration (AMD).

Design: Randomised, prospective, controlled clinical trial.

Methods: Patients suffering from visual loss because of AMD were randomised to either surgery or a control group receiving standard treatment (observation or photodynamic therapy (PDT)).

[Mission and tasks of the Coordination Centres for Clinical Trials].

Coordination Centres for Clinical Trials (Koordinierungszentren für Klinische Studien, KKS) were set up to increase the quality and number of clinical trials in Germany as well as to establish clinical trial training programs in order to improve international recognition of German clinical research. Over the past 6 years, 12 KKS have been set up at the respective universities with a public grant from the Federal Ministry of Education and Research (BMBF). Many non-clinical services have been established to ensure successful co-operation in clinical trials with clinical scientists and industry.

German Paediatric Research Network (PAED-Net).

Clinical trials in children are mandatory to generate data on new drugs as well as on drugs used off-label or for unlicensed indications. The EU Paediatric Regulation introduced in 2007 provides the background, goals, and requirements for pediatric clinical trials. The German Paediatric Network (PAED-Net) was established in 2002 with a public grant from the German Ministry of Education and Research with the aim of developing competence, infrastructure, networking, and education for pediatric clinical trials.

Kinetics and dynamics of the peripheral neurokinin-1 receptor antagonist SLV317 in healthy individuals.

Aims: To investigate the pharmacokinetics and the pharmacodynamic effects in dorsal hand veins of the neurokinin-1 receptor antagonist SLV317.

Methods: In a randomized, double-blind, placebo-controlled cross-over study 19 healthy men received a single oral dose of SLV317 or placebo. Blood samples were collected for analysis of SLV317 plasma concentrations and the inhibition of the venodilator response to substance P was evaluated using the hand vein compliance method.

HEGPOL: randomized, placebo controlled, multicenter, double-blind clinical trial to investigate hepatoprotective effects of glycine in the postoperative phase of liver transplantation [ISRCTN69350312].

Background: Kupffer cell-dependent ischemia/reperfusion (I/R) injury after liver transplantation is still of high clinical relevance, as it is strongly associated with primary dysfunction and primary nonfunction of the graft. Glycine, a non-toxic, non-essential amino acid has been conclusively shown in various experiments to prevent both activation of Kupffer cells and reperfusion injury. Based on both experimental and preliminary clinical data this study protocol was designed to further evaluate the early effect of glycine after liver transplantation.

Adverse events and discomfort in studies on healthy subjects: the volunteer's perspective. A survey conducted by the German Association for Applied Human Pharmacology.

Objective: The various good clinical practice (GCP) guidelines do not define the volunteering subject as an active party. The present survey addresses the volunteer's perception of study-related inconvenience and risk and its impact on their decision to enroll.

Methods: The survey consisted of a questionnaire to be filled out voluntarily and anonymously by healthy subjects who volunteered for enrollment in human pharmacology studies and who had participated in at least one previous study.

[Dealing with adverse effects in phase I trials].

A questionnaire was completed by members of the Association for Applied Human Pharmacology (AGAH) in Germany with the aim of assessing the present situation regarding management of adverse events (AEs). A recommendation for documentation and evaluation of AEs was to be presented after discussion within the AGAH. The questionnaire referred to general questions, documentation of AEs, intensity and causality, coding and serious adverse events (SAE).

Pharmacokinetics, pharmacodynamics and bioavailability of the ACE inhibitor ramipril.

The pharmacokinetics and pharmacodynamics of the prodrug ramipril and its active ACE-inhibiting metabolite ramiprilat were investigated in an open, randomised, three-way cross-over study in 12 healthy male volunteers. Subjects received 2.5 mg ramipril orally, 2.

Differential effects of the novel NO-donating drug pirsidomine and isosorbide dinitrate on the venous vascular bed.

Sixteen healthy male subjects were investigated on four occasions when they received either placebo, 10 mg isosorbide dinitrate (ISDN), or 2.5 or 10 mg pirsidomine, a novel NO-donating drug. A constant-rate iv.

Lack of interaction between ramipril and simvastatin.

Twenty two healthy males participated in a randomised, placebo-controlled, double blind, cross-over study to investigate the influence of simvastatin on the pharmacokinetics of ramipril and its active metabolite (ramiprilat), and on the ACE-inhibiting effect of ramiprilat. During two study periods, each of 7 days, subjects received daily either simvastatin 20 mg at 19.00 h or placebo; ramipril (5 mg) was given on Day 5 of each of the periods.

The pharmacokinetic and pharmacodynamic interactions of ramipril with propranolol.

We have studied the pharmacodynamic effects of ramipril, propranolol, and their combination, as well as the effect of propranolol on the pharmacokinetics of ramipril in 12 healthy men (age 24 (SD 6) y, weight 72 (7) kg). Propranolol and placebo, ramipril and placebo, or propranolol and ramipril were given orally for four days in a crossover, double-blind fashion. The pharmacokinetics of ramipril and ramiprilat were investigated on day 4.

[The use of pulse oximetry in the perioperative monitoring of pediatric patients at risk using the surgical correction of a laparoschisis as an example].

Pulse oximetry has been recently introduced into anesthetic practice as an additional monitoring technique. In contrast to other methods (ECG, inspection, auscultation, blood gas analysis), it immediately detects an impending lack of oxygen, whatever its cause. Therefore, especially in pediatric risk patients, precious time can be saved.