Ranitidine therapy for gastroesophageal reflux disease. Results of a large double-blind trial

In a multicenter, double-blind trial, 284 patients with gastroesophageal reflux disease were evaluated before, during, and after six weeks of treatment with either placebo or ranitidine (150 mg twice daily). Randomization resulted in two comparable patient groups. Ranitidine treatment was significantly more effective than placebo treatment in decreasing the frequency and the severity of heartburn during both daytime and nighttime assessment periods. There was a significant correlation between improvement in heartburn symptoms and decrease in antacid consumption; hence, patients receiving ranitidine consumed significantly fewer antacid tablets. Among patients with endoscopic esophagitis at baseline, the overall change in endoscopic classification after six weeks of therapy was significantly better for the ranitidine-treated patients. The ranitidine-treated group had less evidence of erosions and ulcerations as well as greater healing. There were no differences between the groups with respect to changes in esophageal mucosal sensitivity to acid perfusion or changes in histologic grading of esophageal mucosal biopsy specimens. The ranitidine safety profile was similar to that of previous studies. We conclude that, in patients with gastroesophageal reflux disease, ranitidine therapy, 150 mg twice daily, markedly reduced the heartburn symptoms of reflux disease and significantly improved the endoscopic appearance of the esophageal mucosa.     

Rheumajecta and vasolastine in the treatment of rheumatoid arthritis--the results of a placebo-controlled, double-blind trial of a complementary treatment.

The so called "enzymatic preparations" Rheumajecta and Vasolastine (R & V) belong to the complementary treatments. The preparations have been used for many years in the treatment of patients with rheumatic conditions such as rheumatoid arthritis (RA) in the Netherlands and other countries of Europe, although a proper study showing efficacy was never performed. Therefore a double-blind, placebo-controlled, modified cross-over trial during two periods of 3 months was performed in 34 patients with RA. They were allocated at random to R & V or to placebo injections, all intramuscular. After 3 months of therapy each patient could opt for cross-over in the event of lack of subjective improvement. Clinical assessments including Ritchie's articular index, grip strength, the DUTCH-AIMS questionnaire, ESR and CRP were performed. R & V did not prove to be more effective than placebo. No serious side-effects were seen.     

A randomized,double-blind trial comparing a pulse of 1000 with 250 mg methylprednisolone in rheumatoid arthritis

Summary We compared, in a double blind, randomized, 3-center study, a pulse of 1000 mg methylprednisolone with a pulse of 250 mg methylprednisolone, in patients with active rheumatoid arthritis. Improvement of patients was similar in both groups and lasted up to 3 weeks. Side effects were minor.     

SYST-EUR: a multicenter trial of treatment of systolic hypertension in aged subjects. An initial report]

Syst-Eur is a multicentre placebo-controlled outcome trial, designed by the European Working Party on High Blood Pressure in the Elderly (EWPHE), to investigate the effect of antihypertensive treatment on the incidence of stroke in elderly patients with isolated systolic hypertension (ISH). Eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mmHg with a diastolic blood pressure less than 95 mmHg. The present paper in an interim report on the first 316 patients randomized into this trial. The placebo (N = 170) and active treatment (N = 146) groups were similar at randomization with respect to age (73 +/- 8 years; mean +/- standard deviation), sitting blood pressure (178 +/- 12/85 +/- 7 mmHg), percentage men (34%) and percentage of patients with cardiovascular complications (29%). After randomization blood pressure fell more (p < 0.001) on active treatment than in the placebo group (19 +/- 20/6 +/- 10 mmHg versus 7 +/- 19/1 +/- 10 mmHg for the sitting blood pressure). This first interim report on the Syst-Eur trial demonstrates that a multinational trial in elderly patients with ISH is feasible and that a significant blood pressure difference between the 2 treatment groups can be achieved and maintained. New centres are being recruited in order to randomize a total of 3,000 patients.     

A comparative, double-blind trial with proquazone and naproxen in the treatment of rheumatoid arthritis.

In a double-blind trial lasting 6 months, 36 patients with classical or definity rheumatoid arthritis were divided into two groups, one receiving 3x300 mg proquazone/day and the other 2x250 mg naproxen plus one placebo capsule/day. Efficacy parameters were assessed and laboratory tests performed at regular intervals throughout the trial. Both drugs were well tolerated, in that no abnormal changes were found in the results of laboratory tests in either group, and that drug-related side effects, mainly gastrointestinal disturbances, occurred in just over half the cases in each group. Both drugs improved the Lansbury Index, especially grip strength, walking time, and ESR. Proquazone did significantly better than naproxen in improving ESR and nocturnal pain. More therpaeutic successes were recorded with proquazone than with naproxen in the overall assessment at the end of the trial.     

A controlled trial comparing sulfasalazine, gold sodium thiomalate, and placebo in rheumatoid arthritis

One hundred eight-six patients with active rheumatoid arthritis were evaluated in a double-blind, randomized study that compared treatment with sulfasalazine (SSZ) (2 mg/day), gold sodium thiomalate (GST) (50 mg/week), and placebo (PBO). The 37-week course of therapy was completed by 109 patients. While marked improvement was seen in all 3 treatment groups, the only statistically significant differences between SSZ or GST and PBO were in a decreased erythrocyte sedimentation rate and increased grip strength in the right hand. GST is known to be superior to PBO, and the response of the GST-treated group was similar to that seen in other trials. The response of the PBO group, however, was much greater than in other placebo groups we have studied. SSZ was similar in efficacy to injectable gold, but was better tolerated. Because of adverse drug reactions (most commonly, rash, stomatitis, and proteinuria), 41% of patients were withdrawn from the GST treatment. Untoward drug effects (most frequently, rash and gastrointestinal distress) caused 16% of patients to be withdrawn from SSZ therapy.     

Levamisole in rheumatoid arthritis. Final report on a randomised double-blind study comparing a single weekly dose of levamisole with placebo. Multicentre Study Group.

The therapeutic effect of a single weekly dose of levamisole in patients with rheumatoid arthritis was compared with placebo for 6 months in a 13-centre double-blind controlled study. 281 patients with classic or definite rheumatoid arthritis and active disease were evaluated. A single weekly dose of 150 mg levamisole was superior to placebo in controlling disease activity. A single weekly dose of 50 mg levamisole had an intermediate effect. Adverse reactions occurred in approximately 40% of the patients with 150 mg levamisole and in approximately 20% of the patients with 50 mg levamisole or placebo. In comparison with the classical dosage schedule of levamisole (150 mg on 3 consecutive days each week) a single weekly dose of 150 mg levamisole was found to be slightly less effective but much better tolerated.     

Low-dose methotrexate in rheumatoid arthritis: effect and tolerance. An open trial and a double-blind randomized study

Weekly low-dose Mtx may be considered the preferred drug for the treatment of patients with severe, progressive RA resistant to conventional therapy. The drug is sufficiently safe, provided contra-indications are considered and treatment is carefully supervised. Controlled long-term prospective studies are needed in order to determine whether the drug demonstrably retards progression of the erosions, and to guard against untoward long-term adverse reactions.     

Methotrexate versus azathioprine in the treatment of rheumatoid arthritis. A forty-eight-week randomized, double-blind trial.

We conducted a double-blind, randomized trial comparing azathioprine (AZA) and methotrexate (MTX) in the treatment of patients with rheumatoid arthritis in whom parenteral gold and/or D-penicillamine treatment had been unsuccessful. Patients were randomly assigned to receive either AZA (100 mg daily) or oral MTX (7.5 mg weekly). After 8 weeks, the dosage was increased depending on the clinical improvement. Sixty-four patients were followed up for 48 weeks (33 AZA, 31 MTX). Comparison of values at week 24 with baseline values revealed significant improvement in 12 of 13 disease variables in the MTX group and in 6 of 13 in the AZA group. Comparison between the 2 treatment groups at 24 weeks, by area-under-the-curve analysis, showed significantly more improvement in the MTX group in terms of the swollen joint count, pain score, erythrocyte sedimentation rate, C-reactive protein level, hemoglobin level, thrombocyte level, and disease activity score. A significant overall clinical improvement (disease activity score) was found in 7 of 20 patients treated with AZA and 18 of 30 patients treated with MTX after 24 weeks of therapy, and in 6 of 12 AZA-treated patients and 19 of 25 MTX-treated patients after 48 weeks. The number of withdrawals due to side effects was significantly higher in the AZA group. After 48 weeks, only 12 patients from the AZA group (36%), but 25 from the MTX group (81%), were still using the initial drug. These results demonstrate MTX to be superior to AZA in the treatment of rheumatoid arthritis, with a more rapid clinical improvement which is sustained after 1 year, accompanied by a lower rate of serious adverse reactions.     

Increased bone mass with pamidronate treatment in rheumatoid arthritis. Results of a three-year randomized,double-blind trial

Objective. Osteoporosis is a frequent complication of rheumatoid arthritis (RA). We therefore investigated the effect of oral pamidronate therapy as a specific bone-sparing agent in RA. Methods. The study design was a 3-year randomized, double-blind trial of 300 mg oral pamidronate/day compared with placebo in 105 RA patients. Bone mineral density (BMD) measured at 12-month intervals was the primary efficacy parameter. Results. In 3 years, lumbar spine and forearm BMD increased significantly in the pamidronate-treated group (by 8.4 ± 6.9% [mean ± SEM] [P < 0.0001] and 5.2 ± 6.5% [P < 0.005], respectively), compared with nonsignificant changes in the placebo-treated patients (increase of 0.6 ± 5.2% and decrease of 1.2 ± 5.8%, respectively). Femoral neck BMD increased in the pamidronate-treated group (by 2.6 ± 8.6%) and decreased significantly in the placebo-treated group (by 4.0 ± 1.3% [P < 0.005]). The changes in BMD with time at all 3 measurement sites were significantly different between the treatment groups (P < 0.0001). Changes in radiographic signs of joint damage and in disease activity were similar in the 2 groups. Conclusion. The present study provides the first evidence that long-term treatment with an orally administered bisphosphonate overcomes bone loss and increases bone mass when compared with placebo. This finding may have significance with regard to the treatment of patients with RA.     

Final report on a placebo-controlled, double-blind, randomized, multicentre trial of cyclosporin treatment in active chronic Crohn's disease

In a previous report we published the immediate results of a 3-month placebo-controlled trial (n = 34) showing that cyclosporin (n = 37) has a beneficial therapeutic effect in active chronic Crohn's disease. Here we report on the final outcome of the patients. During the 3-month tapering-off period eight initially improved patients (36%) in the cyclosporin group worsened, as did six (55%) in the placebo group. The therapeutic gain of cyclosporin treatment was consistently significant during this period. It ranged from 22% to 25% (95% confidence limits, 2-46%). An outcome ranking showed that 7 patients of the cyclosporin group (19%) were substantially improved, 7 (19%) moderately improved, and 23 (62%) not improved after the tapering off. In contrast, no significant differences were seen during the 6-month follow-up period. Four patients of the cyclosporin group (11%) were substantially improved, 3 (8%) moderately improved, and 30 (81%) not improved at final follow-up. Significant interactions between cyclosporin and prednisolone treatment were demonstrated both at the end of the initial treatment period and at the end of the tapering-off period. We conclude that a short course of cyclosporin treatment does not result in long-term improvement in active chronic Crohn's disease.     

Lymphoid irradiation in intractable rheumatoid arthritis. A double-blind, randomized study comparing 750-rad treatment with 2,000-rad treatment

Twenty patients with intractable rheumatoid arthritis were treated with 750-rad or 2,000-rad lymphoid irradiation in a randomized double-blind comparative study. Over a 12-month followup period, there was a significant improvement in 4 of 7 and 6 of 7 standard parameters of disease activity following treatment with 750 rads and 2,000 rads, respectively. Transient, short-term toxicity was less frequent with the lower dose. In both groups, there was a sustained peripheral blood lymphopenia, a selective depletion of T helper (Leu-3a+) lymphocytes, and reduced in vitro mitogen responses. These changes did not occur, however, in synovial fluid. These results suggest that 750-rad lymphoid irradiation is as effective as, but less toxic than, that with 2,000 rads in the management of patients with intractable rheumatoid arthritis.