Solumedrol Treatment for Severe Sepsis in Humans with a Blunted Adrenocorticotropic Hormone-Cortisol Response: A Prospective Randomized Double-Blind Placebo-Controlled Pilot Clinical Trial

2021 ◽  
pp. 088506662110388
Author(s):  
Divya Birudaraju ◽  
Sajad Hamal ◽  
John A. Tayek
Keyword(s):  
Blood Pressure ◽  
Clinical Trial ◽  
Adrenocorticotropic Hormone ◽  
Serum Cortisol ◽  
High Dose ◽  
Cortisol Response ◽  
Acth Stimulation ◽  
Double Blind ◽  
Significant Difference ◽  
To Receive

Purpose To test the benefits of Solumedrol treatment in sepsis patients with a blunted adrenocorticotropic hormone (ACTH)-cortisol response (delta <13 µg/dL) with regard to the number of days on ventilator, days on intravenous blood pressure support, length of time in an intensive care unit (ICU), 14-day mortality, and 28-day mortality. The trial was prospective, randomized, and double-blind. As part of a larger sepsis trial, 54 patients with sepsis had an intravenous ACTH stimulation test using 250 µg of ACTH, and serum cortisol was measured at times 0, 30, and 60 min. Eleven patients failed to increase their cortisol concentration above 19.9 µg/dL and were excluded from the clinical trial as they were considered to have adrenal insufficiency. The remaining 43 patients had a baseline cortisol of 32 ± 1 µg/dL increased to 38 ± 3 µg/dL at 30 min and 40 ± 3 at 60 min. All cortisol responses were <12.9 µg/dL between time 0 and time 60, which is defined as a blunted cortisol response to intravenous ACTH administration. Twenty-one were randomized to receive 20 mg of intravenous Solumedrol and 22 were randomized to receive a matching placebo every 8 h for 7-days. There was no significant difference between the two randomized groups. Data analysis was carried out bya two-tailed test and P < .05 as significant. Results Results: The mean age was 51 ± 2 (mean ± SEM) with 61% female. Groups were well matched with regard to APACHE III score in Solumedrol versus placebo (59 ± 6 vs 59 ± 6), white blood cell count (18.8 ± 2.2 vs 18.6 ± 2.6), and incidence of bacteremia (29 vs 39%). The 28-day mortality rate was reduced in the Solumedrol treated arm (43 ± 11 vs 73 ± 10%; P < .05). There was no change in days in ICU, days on blood pressure agents, or days on ventilator. Seven days of high-dose intravenous Solumedrol treatment (20 mg every 8 h) in patients with a blunted cortisol response to ACTH was associated with an improved 28-day survival. This small study suggests that an inability to increase endogenous cortisol production in patients with sepsis who are then provided steroid treatment could improve survival.

Double-blind, multicenter, randomized trial to compare the effect of two doses of adrenocorticotropic hormone versus placebo in controlling delayed emesis after high-dose cisplatin in adult patients with cancer.

1997 ◽  
Vol 15 (6) ◽  
pp. 2467-2473 ◽  
Author(s):  
R Passalacqua ◽  
G Cocconi ◽  
C Caminiti ◽  
V Silingardi ◽  
M A Bella ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Adrenocorticotropic Hormone ◽  
Serum Cortisol ◽  
High Dose ◽  
Delayed Emesis ◽  
Double Blind ◽  
Acute Emesis ◽  
Patients With Cancer ◽  
To Receive ◽  
Different Doses

PURPOSE To compare, in a double-blind, placebo-controlled, randomized trial, the efficacy of two different doses of the depot formulation of adrenocorticotropic hormone (ACTH) in controlling delayed emesis after cisplatin. PATIENTS AND METHODS One hundred fifty-two patients were enrolled onto the study. On day 1, all patients received cisplatin (60 to 120 mg/m2) and a combination of dexamethasone 20 mg plus ondansetron or metoclopramide to prevent acute emesis. On day 2 (24 hours after cisplatin administration), patients were randomized to receive placebo, or ACTH 1 mg intramuscularly (I.M.), or ACTH 2 mg I.M. plus one additional dose of 1 mg on day 4. Details of vomiting, nausea, and adverse effects were recorded daily for every 24-hour period from day 2 to day 6. In a subset of patients, serum cortisol levels were measured between 20 and 72 hours after cisplatin administration. RESULTS One hundred fifty patients were assessable. Over the 5 days of the study, delayed vomiting occurred less frequently in the patients treated with ACTH 2 mg plus 1 mg than in those treated with ACTH 1 mg or placebo (28%, 38%, and 65%, respectively; P = .001). The greatest observed differences were seen on days 2 (24 to 48 hours; P = .01) and 3 (48 to 72 hours; P = .01). On days 4, 5, and 6 (96 to 144 hours), no significant differences were observed among the three arms. The severity of delayed emesis expressed as the mean number of emetic episodes per day was 0.48, 0.70, and 0.80, respectively (P = .002). Patients treated with the higher dose of ACTH had the least nausea on day 3 (P = .02) and day 4 (P = .03). Adrenal cortisol secretion rapidly increased after ACTH injection, but was suppressed for approximately 44 hours in the placebo group. Toxicity was mild and transient in all groups. CONCLUSION ACTH reduces the incidence and severity of delayed vomiting and nausea after cisplatin. A dose of 2 mg 24 hours after cisplatin is better than one of 1 mg. Whether the activity of ACTH is mediated only by adrenal corticosteroids needs to be verified.

The Characterization Of Adrenal Insufficiency and Identification Of Its Risk Factors In Patients With Plasma Cell Dyscrasias

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5376-5376
Author(s):  
Nadim K Choudhury ◽  
Alice Levine ◽  
Ajai Chari
Keyword(s):  
Board Of Directors ◽  
Serum Cortisol ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cortisol Response ◽  
Inclusion Criteria ◽  
Acth Stimulation Test ◽  
Acth Stimulation ◽  
Advisory Committees ◽  
Al Amyloid

Abstract Background The introduction of proteasome inhibitors and immunomodulatory agents to treat patients with multiple myeloma (MM) and AL amyloidosis have greatly improved survival in these patients and allowed for the use of relatively steroid-sparing regimens.  However, 40 mg of dexamethasone is still more than 50 times basal glucocorticoid secretion.  Therefore, intermittent dosing of dexamethasone, the longest acting oral corticosteroid, while beneficial in terms of reducing side effects from chronic glucocorticoid excess, may still compromise endogenous adrenal gland function. Our hypothesis was that prolonged, intermittent use of high dose steroids can result in adrenal insufficiency in some patients.  The aim of this retrospective study was to determine the characteristics of patients who developed AI. Methods Inclusion criteria for this retrospective case series were patients who had plasma cell disorders and who had been diagnosed with AI based on symptoms concordant with a low serum cortisol level (normal 6.7 - 22.6 mcg/dL), an inadequate cortisol response on an ACTH stimulation test, or for those patients with a fulminant clinical presentation - a rapid clinical improvement upon initiation of low dose maintenance corticosteroid replacement therapy. Exclusion criteria were patients who had serum cortisol levels checked in the setting of recent administration of corticosteroids, who had an adequate cortisol response to an ACTH stimulation test in the setting of a normal basal cortisol level, or who did not require replacement therapy to achieve resolution of symptoms. Results Sixteen patients met the inclusion criteria over a span of approximately 18 months.  Two patients had AL amyloidosis, 12 had MM, and 2 had both.  3 patients were excluded. The median age of patients at the time of AI diagnosis was 61.5 (Range: 44-76). The median number of steroid-containing cycles taken before the diagnosis of AI was 10.5 (Range: 4-50) over a median of 27 months (Range: 3-129). The median cumulative steroid consumption was 1000 mg of dexamethasone. Of note, the 2 primary AL amyloid patients only received 4 and 8 cycles of corticosteroids and a lower amount of cumulative corticosteroids, 768 and 800 mg, respectively prior to being diagnosed with AI. The symptoms and signs of AI at the time of diagnosis included fatigue (88% of patients), diarrhea (56%), hypotension (56%), orthostasis (44%) and weight loss (31%).  Other symptoms that appeared in multiple patients included nausea, diffuse myalgia, fever, and cardiovascular shock. The median time between the last steroid dose and the serum cortisol assay was 7 days (Range: 1-62), which resulted in a median serum cortisol of 3.7 mcg/dL (Range 0.5-21 mcg/dL). Of the seven patients who had serum ACTH levels checked, only one patient (with primarly AL amyloid) had an elevated ACTH of 68 (normal 12-46 pg/mL), suggesting a possible component of primary AI. Five patients also underwent ACTH stimulation tests, two of which demonstrated an inappropriate response, defined as a lower rise in serum cortisol than expected. To treat AI, patients received about 15-20 mg of hydrocortisone (equivalent to 0.6- 0.8 mg of dexamethasone) on days not receiving steroids for treatment of their malignancy. 2 patients requiring pressors for shock also required stress dose steroids.  For patients with AI symptoms, normalization of hypotension and weight required a median of 9 days (Range 2-43 days) and 2 months (Range 0.3-20 months) respectively to return to their pre-AI levels. Orthostasis resolved after a median of 33 days (Range: 22-72 days), however, orthostatics were not checked at each clinic visit. Conclusions Our study shows that chronic treatment with even intermittent high-dose steroids can lead to AI, typically characterized by such nonspecific symptoms as fatigue, diarrhea, and dizziness occurring 3-4 days after the last exogenous steroid administration. Unfortunately, the debilitating presentation of some patients with orthostasis/hypotension as well as an already demanding schedule for chemotherapy visits makes optimal cortisol and ACTH stimulation testing challenging. A high index of suspicion for AI is required to initiate diagnostic and therapeutic interventions in a timely fashion to minimize the morbidity and mortality of this condition. Disclosures: Chari: Millenium : Membership on an entity’s Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Onyx: Membership on an entity’s Board of Directors or advisory committees.

scholarly journals Comparison of the effects of sertraline and L-carnitine on intradialytic hypotension; a double blind clinical trial

2020 ◽  
Vol 9 (3) ◽  
pp. e22-e22
Author(s):  
Sanaz Jamshidi ◽  
Sepideh Hajian ◽  
Nafiseh Rastgoo ◽  
Navid Mohammadi
Keyword(s):  
Blood Pressure ◽  
Clinical Trial ◽  
Intradialytic Hypotension ◽  
Duration Of Treatment ◽  
Double Blind ◽  
Double Blind Clinical Trial ◽  
Significant Difference ◽  
Blood Pressures ◽  
Pre Treatment ◽  
Positive Effect

Introduction: Although some studies have reported the positive effect of sertraline and L-carnitine on intradialytic hypotension (IDH), a common complication of dialysis, however the results are controversial. Objectives: The aim of this study was to compare the effects of sertraline and L-carnitine on blood pressure in patients with chronic renal failure who were undergoing dialysis. Patients and Methods: This double-blind clinical trial was conducted on 32 hemodialysis patients who suffered from IDH in more than 50% of dialysis sessions. Patients were randomly divided into two groups of sertraline (50 mg daily) and L-carnitine (1000 mg daily), with 16 patients in each group. Duration of treatment was four weeks, then patients were followed up for additional three weeks. The changes in patients’ blood pressure were monitored in each group and the results compared between the two groups. Results: Of all, 18 patients (56%) were female, 14 patients (44%) were male, and their mean (SD) age was 60±15 years. At the end of the study, mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP), and mean arterial pressure (MAP) were significantly increased in both the sertraline and L-carnitine groups (P<0.05). In addition, nadir SBP, nadir DBP, and nadir MAP in each group were significantly increased compared to pre-treatment period (P<0.001). An increase of more than 5 mm Hg in SBP, DPB, and MAP was observed in half of the subjects in the sertraline group and more than two-thirds of the patients in the L-carnitine group, however there was no significant difference between the two groups (P>0.05). Conclusion: The findings of this study showed that the administration of sertraline or L-carnitine for one month could significantly increase SBP, DBP, MAP, and nadir blood pressures in dialysis patients suffering from IDH during dialysis sessions because there was no significant difference between the two drugs.

The Effects of a Caffeine Placebo and Experimenter Expectation on Blood Pressure, Heart Rate, Well-Being, and Cognitive Performance

2001 ◽  
Vol 6 (1) ◽  
pp. 15-25 ◽  
Author(s):  
Harald Walach ◽  
Stefan Schmidt ◽  
Yvonne-Michelle Bihr ◽  
Susanne Wiesch
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cognitive Task ◽  
Well Being ◽  
Control Group ◽  
Double Blind ◽  
Main Effect ◽  
The Difference ◽  
Being There ◽  
To Receive

We studied the effect of experimenter expectations and different instructions in a balanced placebo design. 157 subjects were randomized into a 2 × 4 factorial design. Two experimenters were led to expect placebos either to produce physiological effects or not (pro- vs. antiplacebo). All subjects except a control group received a caffeine placebo. They were either made to expect coffee, no coffee, or were in a double-blind condition. Dependent measures were blood pressure, heart rate, well-being, and a cognitive task. There was one main effect on the instruction factor (p = 0.03) with the group “told no caffeine” reporting significantly better well-being. There was one main effect on the experimenter factor with subjects instructed by experimenter “proplacebo” having higher systolic blood pressure (p = 0.008). There was one interaction with subjects instructed by experimenter “proplacebo” to receive coffee doing worse in the cognitive task than the rest. Subjects instructed by experimenter “antiplacebo” were significantly less likely to believe the experimental instruction, and that mostly if they had been instructed to receive coffee. Contrary to the literature we could not show an effect of instruction, but there was an effect of experimenters. It is likely, however, that these experimenter effects were not due to experimental manipulations, but to the difference in personalities.

Efficacy of Aloe vera/ Plantago Major Gel in Diabetic Foot Ulcer: A Randomized Double-Blind Clinical Trial

2019 ◽  
Vol 16 (2) ◽  
pp. 223-231 ◽  
Author(s):  
Younes Najafian ◽  
Zahra M. Khorasani ◽  
Mona N. Najafi ◽  
Shokouh S. Hamedi ◽  
Marjan Mahjour ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Diabetic Foot ◽  
Intervention Group ◽  
Aloe Vera ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Control Group ◽  
Plantago Major ◽  
Double Blind ◽  
Significant Difference

Background:Diabetic foot ulcer (DFU) is one of the most common complications of diabetic patients. Mostly, non-healing DFU leads to infection, gangrene, amputation and even death. High costs and poor healing of the wounds need a new treatment such as alternative medicine. So, the aim of this study was to evaluate the efficacy of Aloe vera/ Plantago major gel (Plantavera gel) in healing of DFUMethods:Forty patients with DFU enrolled in a double-blind randomized clinical trial. The patients who were randomly assigned into the intervention group (n = 20), received topical Plantavera gel in addition to the routine cares, whereas the patients in the control group (n = 20), received topical Placebo gel in addition to the routine cares. Intervention was done twice a day for 4 weeks in the both groups. Photography and an evaluation of DFU healing were conducted by a checklist and then were scored at baseline and at the end of each week. The collected data was analyzed by SPSS software.Results:At the end of the study, there was a significant difference between the two groups in terms of total ulcer score (P<0.001) and Plantavera gel significantly reduced the ulcer surface comparing with the control group (P=0.039). However, there was not a significant difference between the two groups (P=0.263) in terms of the ulcer depth. During this study, no side effect was observed for Plantavera gel in the intervention group.Conclusion:Topical Plantavera gel seems to be an effective, cheap and safe treatment. Of course, further studies are required to confirm the properties of the wound healing of this gel.

Relief of pain and trismus in patients treated with naproxen or acetylsalicylic acid after tonsillectomy

1988 ◽  
Vol 102 (1) ◽  
pp. 39-42 ◽  
Author(s):  
S. Kristensen ◽  
K. Tveteraas ◽  
P. Hein ◽  
H. B. Poulsen ◽  
K. E. Outzen
Keyword(s):  
Clinical Trial ◽  
Acetylsalicylic Acid ◽  
Pain Intensity ◽  
Sleep Disturbances ◽  
Significant Positive Correlation ◽  
Controlled Trial ◽  
Double Blind ◽  
Treatment Groups ◽  
Significant Difference ◽  
Therapeutic Gain

AbstractThe pain-relieving efficacy of naproxen and acetylsalicylic acid (ASA) in tonsillectomized patients was compared in a double blind parallel clinical trial comprising 83 patients, among whom 42 were treated with naproxen and 41 with ASA. The patients were treated post-operatively for two days with either naproxen suppositories 500 mg. twice, or ASA effervescent tablets 1000 mg. three times, daily.The therapeutic gain was evaluated by recording the intensity of pain, reduced ability to open the mouth (trismus), consumption of supplementary analgesic (parcetamol), and pain-related sleep disturbances.The statistical analysis of the results revealed no differences in pain intensity, consumption of additional analgesics or pain-related sleep disturbances in the two treatment groups. A considerable degree of trismus was demonstrated in most of the tonsillectomized patients. This reduced ability to open the mouth was gradually overcome in the naproxen group while it remained unchanged in the ASA group, however, no statistical significant difference could be demonstrated. Additionally, no significant positive correlation between pain intensity and trismus was proven. The pain-relieving effect, however, was unsatisfactory in both the naproxen and the ASA group, and clinical controlled trial studies of alternative analgetics in tonsillectomized patients are still to be encouraged.

scholarly journals Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of the β-Lactamase Inhibitor Vaborbactam (RPX7009) in Healthy Adult Subjects

2016 ◽  
Vol 60 (10) ◽  
pp. 6326-6332 ◽  
Author(s):  
David C. Griffith ◽  
Jeffery S. Loutit ◽  
Elizabeth E. Morgan ◽  
Stephanie Durso ◽  
Michael N. Dudley
Keyword(s):  
Plasma Clearance ◽  
Healthy Adult ◽  
Phase 1 ◽  
High Dose ◽  
Double Blind ◽  
Time Curve ◽  
Content Type ◽  
Multiple Doses ◽  
To Receive ◽  
Lactamase Inhibitor

ABSTRACTVaborbactam (formerly RPX7009) is a member of a new class of β-lactamase inhibitor with pharmacokinetic properties similar to those of many β-lactams, including carbapenems. The pharmacokinetics and safety of vaborbactam were evaluated in 80 healthy adult subjects in a first-in-human randomized, placebo-controlled, double-blind, sequential single- and multiple-ascending-dose study. A total of 10 dose cohorts were enrolled in the study, with 6 subjects randomized to receive 250 to 2,000 mg of vaborbactam and 2 subjects randomized to receive placebo in each cohort. Maximum concentrations for vaborbactam were achieved at the end of the 3-h infusion. Vaborbactam exposure (Cmaxand area under the concentration-time curve [AUC]) increased in a dose-proportional manner following multiple doses. There was no evidence of accumulation with multiple doses, consistent with the terminal half-life of ∼2 h. Both the volume of distribution (Vss) and plasma clearance were independent of dose. For the 2,000-mg dose, the plasma clearance was 0.17 ± 0.03 liters/h, the AUC from 0 h to infinity (AUC0–∞) was 144.00 ± 13.90 mg · h/liter, and theVsswas 21.80 ± 2.26 mg · h/liter. Urinary recovery was 80% or greater over 48 h across all dose groups. No subjects discontinued the study due to adverse events (AEs), and no serious AEs (SAEs) were observed. All AEs were mild to moderate and similar among the vaborbactam- and placebo-treated subjects, with mild lethargy as the only unique AE reported with the high dose of vaborbactam. Overall, this study revealed the safety, tolerability, and pharmacokinetic profile of vaborbactam and formed the basis for advancement into patient studies in combination with meropenem, including treatment of patients with carbapenem-resistantEnterobacteriaceae(CRE) infections. (This study is registered at ClinicalTrials.gov under identifier NCT01751269.)

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