The METEX study (Methotrexate versus Expectant management) Methotrexate versus expectant management in women with ectopic pregnancy Background The incidence of ectopic pregnancy (EP) is approximately 1-2 % of all pregnancies. An early diagnosis is possible by transvaginal sonography (TVS) in combination with serum hCG measurements. As a consequence, the clinical presentation of EP has changed from a life threatening disease, necessitating emergency surgery, to a more benign condition in sometimes even asymptomatic patients for which non-surgical treatment options are available, i.e. medical treatment or expectant management. In the medical treatment of EP, systemic methotrexate is the drug of choice. In several randomised controlled trials systemic methotrexate has been shown to be an effective treatment in selected patients with EP. Expectant management has been practiced, based on the acknowledgement that the natural course of many early EPs is a self limiting process, ultimately resulting in tubal abortion or reabsorption. For both treatment regimens follow up of serum hCG is mandatory to detect impending treatment failure. Ten percent of women presenting with suspected EP have low and plateauing serum hCG concentrations. These women are often treated with systemic methotrexate. However, there is no evidence on the effects of treatment in this particular subgroup of women Objective To study whether in women with EP with low but plateauing serum hCG concentrations treatment with systemic methotrexate in a single dose intramuscular regimen is superior over expectant management in terms of treatment success, future pregnancy, health related quality of life and costs.
Study-design Multicenter randomised controlled trial in four participating centers in The Netherlands. Population All hemodynamically stable patients ≥ 18 years with either on TVS a visible EP and a plateauing serum hCG concentration < 1,500 IU/L or with a pregnancy of unknown location (PUL) and a plateauing serum hCG concentration < 2,000 IU/L (persisting PUL) will be eligible for the trial. Patients with a viable EP, signs of tubal rupture or active intra abdominal bleeding, or a contra-indication for methotrexate will not be included. Randomisation will be carried out by an internet based randomisation. Intervention and follow up Systemic methotrexate in a single dose intramuscular regimen (1 mg/kg body weight) will be compared with expectant management in an outpatient clinical setting. Serum hCG levels will be monitored weekly. In case of inadequately declining serum hCG concentrations and/or clinical symptoms treatment (methotrexate or surgery) will be installed. Quality of Life will be assessed before, during and after treatment by questionnaires. Future fertility will be assessed by questionnaires after 6, 12, 18 and 24 months.
Outcome measures and analysis The primary outcome measure is an uneventful decline of serum hCG to an undetectable level. Secondary outcomes are number of (re)interventions (additional methotrexate and/or surgery), treatment complications, health related quality of life, future fertility, and financial costs. The analysis wil be performed according to the intention to treat principle. Moreover, patients’ preferences will be assessed.
Estimated patient’s effort and risks In both treatment arms patients are at risk of tubal rupture and/or active bleeding. Methotrexate has possible side effects. After methotrexate treatment patients are advised not to conceive during 3 months. Patients are requested to fill in questionnaires to assess quality of life before, during and after treatment. Furthermore, patients will be contacted by telephone or mail after 6, 12, 18, 24 months to assess her future fertility. E-mail: [email protected]
In this study, we examine the distribution of revenues for a comprehensive sample of newdrugs introduced into the United States during the period, 1988 to 1992. In earlier research, weexamined the returns to R&D for the U.S. new drug introductions during the 1970s and early "The Distribution of Sales from Pharmaceutical Innovation" 1980s.[1,2] One of the key findings was that the
Journal of Metals, Materials and Minerals, Vol.22 No.2 pp.13-18, 2012 Cetirizine Dihydrochloride Tablets Comprising Two Different Lubricants with Highly Loaded Colloidal Silicon Dioxide Prachya KATEWONGSA1,a, Thawatchai PHAECHAMUD1,b,* 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Abstract Recently, the fast disintegrating tablet (FDT)