Tag Archives: Clostridium difficile Clincial Trials

Learn More About Clostridium difficile (C.diff., C.difficile) infection and Recurrent CDI Clinical Trials In Progress

 

 

 

The C Diff Foundation has implemented a global campaign to raise awareness of Clostridium difficile infection (C.difficile) clinical trials, clinical studies, clinical research and observational studies evaluating interventions for C. difficile prevention, treatments, and environmental safety.

In the USA: Nearly half a million Americans suffer from Clostridium difficile (C. diff.) infections in a single year according to a study released in 2015 by the Centers for Disease Control and Prevention (CDC). Approximately 29,000 patients died within 30 days of the initial diagnosis of C. difficile. Of those, about 15,000 deaths were estimated to be directly attributable to C. difficile infections making C. difficile a very important cause of infectious disease death in the United States.

“Clostridium difficile infections are not only the most common cause of healthcare-acquired infections in the United States but also very common in the community in younger patients who previously were thought to be less susceptible to C. difficile. The rate of recurrent C. difficile infections is increasing tremendously and this increase is higher than the rate of primary C. difficile infections,” stated Sahil Khanna, MD, Assistant Professor of Medicine Division of Gastroenterology and Hepatology, Director of the C. difficile Clinic, Fecal Microbiota Transplantation program and C. difficile related Clinical Trials, Mayo Clinic, Rochester, MN.

Dr. Khanna also added, “It is imperative and important for clinical trials to be done to advance the development of new treatments, new medications, and new ways to prevent and treat Clostridium difficile infections.”

Individuals volunteer to participate in clinical trials in hopes of improving their own health, to access treatments that might not be available otherwise, often because they are new and not yet widely available. They help others by contributing to advances in medicine. There can also be potential risks participating in clinical trials and clinical studies. All of the known risks associated with a particular trial and or study will be discussed during the informed consent process. It will be thoroughly explained in the informed consent document that a volunteer will receive from the research staff prior to participating in any study.

To learn more about clinical research (e.g., Clostridium difficile, C.difficile) visit the U.S. Food and Drug Administration http://www.fda.gov or telephone 1-800-835-4709, The National Institutes of Health (NIH) http://www.nih.gov and ClinicalTrials.gov.

“Clinical trials are vital to improving our knowledge about how best to prevent and treat C. difficile infections. Informing patients of clinical trials is important, and in recent years several clinical trials have led to significant improvements in the treatments available for patients with C. difficile infections,” stated Mark Wilcox, MD, FRCPath, Consultant Microbiologist, Head of Microbiology and Academic Lead of Pathology Leeds Teaching Hospitals, Professor of Medical Microbiology University of Leeds Institute of Biomedical and Clinical Sciences, Lead on Clostridium difficile for Public Health England, UK.

About the U.S. Food and Drug Administration (FDA):
The FDA is responsible for protecting the public health by assuring that foods are safe, wholesome, sanitary and properly labeled; ensuring that human and veterinary drug, and vaccines and other biological products and medical devices intended for human use are safe and effective. FDA’s responsibilities extend to the 50 United States, the District of Columbia, Puerto Rico, Guam, the Virgin Islands, American Samoa, and other U.S. territories and possessions.

About the National Institutes of Health (NIH):
The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the nation’s medical research agency making important discoveries that improve health and save lives.

About ClinicalTrials.gov
ClinicalTrials.gov is a Web-based resource that provides patients, their family members, health care professionals, researchers, and the public with easy access to information on publicly and privately supported clinical studies on a wide range of diseases and conditions.

Rebiotix Features Three Posters Highlighting RBX2660 Clinical and Microbiome Data at ID Week™ 2017 in San Diego, October 4th – 8th

Positive Topline Data from Open-Label Phase 2 Trial of RBX2660 in Recurrent Clostridium
difficile to be Presented for First Time

 

 

 

Rebiotix Inc., a clinical-stage microbiome company focused
on harnessing the power of the human microbiome to treat challenging diseases, today announced that three posters highlighting RBX2660 clinical and microbiome data will be featured at ID Week™ 2017 in San Diego, Oct. 4th to the 8th.

The posters describe clinical findings that highlight the key changes to
the human microbiome profiles of patients who received RBX2660, Rebotix’s Phase 3 drug candidate.

For the first time, researchers will discuss findings from the open-label Phase 2 trial of RBX2660 for the prevention of recurrent Clostridium difficile (C. diff.) infection. Data indicated that RBX2660 was well tolerated and achieved the primary efficacy endpoint of preventing C. diff. recurrence; patients treated with RBX2660 exhibited a treatment success rate of 78.8% compared with a historical control of 51.8% (p<0.0001, N=242). These results demonstrate a 55% reduction in recurrence for those patients treated with RBX2660 compared to the historical controls reflecting standard-of-care antibiotics today.

RBX2660 is currently being evaluated in a multinational Phase 3 clinical trial for the prevention of recurrent C. diff.  Researchers will also be presenting two posters on the microbiome analyses of the Phase 2B  randomized, placebo-controlled, double-blind clinical trial of RBX2660. The analyses, utilizing leading  edge genomic sequencing technology to measure the patient’s microbiome, provide measurable  evidence of RBX2660’s rehabilitative effect on human microbiome profiles of patients who were successfully treated with Rebiotix’s microbiota drug technology.

“The clinical potential of RBX2660 has been highlighted in multiple trials, including our recently
completed open-label Phase 2 study, and the data being presented at ID Week enables us to more fully understand RBX2660’s ability to rehabilitate a dysbiotic intestinal microbiome,” commented Lee Jones, president and CEO of Rebiotix. “These findings are important in that not only can we observe the clinical 2 effect of RB X2660, such as in the open-label Phase 2 study, but by analyzing the microbiota of RBX2660-treated patients, we can see how the microbiome changes in response to RBX2660 treatment and how those changes correlate to treatment success and to the microbiomes of healthy individuals.”

The first poster (#1863; to be presented Friday, Oct. 6th), titled RBX2660 is Safe, Superior to Antibiotic- Treated Controls for Preventing Recurrent Clostridium difficile, and May Rehabilitate Patient Microbiomes:  Open Label Trial Results, reported data from an open-label Phase 2 study of RBX2660 that included 242 subjects. Data from the study indicated that RBX2660’s efficacy in preventing recurrent Clostridium difficile infection (rCDI) was higher (78.8%) than CDI-free rates in the Historical Control Group (51.8%, p<0.0001). The reduction in recurrence of C. diff between these two arms is approximately 55%. Moreover, the safety profile of RBX2660 was consistent with results from previous clinical trials, and microbiota analysis suggested that RBX2660 may rehabilitate patient microbiota as RBX2660-treated subjects’ microbiomes were significantly altered compared to baseline and more closely resembled the RBX2660 microbiome profile than at baseline (p<0.05 by Dirichlet multinomial Wald-type pairwise hypothesis test).

The second poster (#1267; to be presented Saturday, Oct, 7th), titled Successful Response to
Microbiota-Based Drug RBX2660 in Patients with Recurrent Clostridium Difficile Infection is Associated with More Pronounced Alterations in Microbiome Profile, involved an analysis of 58 patients whose stool samples were collected in the randomized Phase 2B clinical trial to determine the effect of RBX2660 on rCDI patient microbiomes. 16s RNA sequencing analyses of patients’ microbiomes indicated that RBX2660 treatment shifted the relative microbiome densities, with taxa-specific increase in Bacteroidia, Clostridia, and decrease in Gamma-proteobacteria abundance. Importantly, a larger shift from baseline microbiome was seen in responders to RBX2600 compared to non-responders, and RBX2660 treatment appears to increase microbiome diversity.

 

The third poster (#1870; to be presented Saturday, Oct. 7th), titled Microbiome Profile is Distinct in Patients with Successful Response to Microbiota-Based Drug RBX2660 Relative to Placebo Responders involved a sub-analysis of 57 patients who participated in the randomized Phase 2B clinical trial of RBX2660. 16s rRNA sequencing analysis was used to compare the microbiome changes from baseline of patients classified as responders to RBX2660 vs placebo. Investigators determined that RBX2660 treatment for rCDI is associated with greater changes in patient microbiomes than placebo treatment. Notably, at 7, 30 and 60 days, microbiomes from RBX2660-treated patients had high Kullback-Leibler divergence from baseline and significantly different means from baseline (p<0.001). Further, active responders trended toward higher Bacteroides and lower Gamma-proteobacteria and Bacilli after treatment, both of which are characteristic of a healthier microbiome. According to the 3 researchers, these changes are consistent with the hypothesis that RBX2660 can restore a healthier microbiome in rCDI patients.

Rebiotix, Inc. funded all three studies.

For More Information About Rebiotix Please

Click On the Following Link:

http://www.rebiotix.com

Two UK Researchers, Prof.Alistair Leanord and Dr. David Enoch, Present CDI Data At the 27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID)

Repeated infection with the bacterium Clostridium difficile (C. difficile, C.diff.), which causes abdominal pain, fever, diarrhea is linked to higher death rates, as well as having a significant impact on health services in terms of cost and hospital beds occupied.

In the first of two presentations at the 27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) (tomorrow (Saturday), Professor Alistair Leanord, from Glasgow University, UK, will say that in Scotland the extra impact on the health service from C. difficile infections amounted to 10,600 bed days a year. “This is the equivalent to a 30-bed hospital ward being fully occupied all year,” he will say.

He will tell the congress that the (median) average cost of a patient with C. difficile infection was £7,500 (€8,600 approximately) compared to £2,800 (€3,200 approx) for patients with other medical conditions. In Scotland over a one year period, from October 2015 to October 2016, there were 1,150 cases of C. difficile infection in patients aged 15 and over. This cost the National Health Service (NHS) in Scotland a total of £8,650,000. Out of this amount, the additional costs of treating C. difficile infection, over and above the basic cost of a hospital bed and normal medical care, was £1,955,000. The calculations were carried out at Strathclyde University, which is part of the Scottish Healthcare Associated Infection Prevention Institute (SHAIPI) research consortium.

Until now, little has been known about the impact on health service resources from C. difficile infections, and on patients in terms of recurrence of infection, readmission to hospital, length of stay and death rates.

Prof. Leanord and his colleagues in Scotland identified 3,304 patients with C. difficile in Scottish hospitals between 2010 and 2013 and matched them with 9,516 patients who did not have the infection (the control group). Approximately two-thirds of the C. difficile patients acquired the infection in hospital.

They found that patients with C. difficile infection had more than double the risk of dying from any cause within two months of being admitted to hospital; nearly a third of all C. difficile cases (29%) died within two months compared to 14% of patients in the control group. Patients with C. difficile stayed in hospital a (median) average 9.7 days longer than the patients without the infection. Of the 1,712 C. difficile patients who were discharged from hospital within 30 days of the first episode of infection, 59% were readmitted within six months; of the 626 cases discharged more than 30 days after the first episode 53% were readmitted within six months. Few of these re-admissions were directly related to C. difficile infection.

“However, nearly a sixth of patients (14%) who were cured of the initial infection recurred within three months, and nearly one third of them (29%) had a second recurrence within a year,” says Prof. Leanord.

Older people were more vulnerable to a recurrence. Among the patients with C. difficile infection, 22% were aged 85 or over, and patients aged 75 and over had approximately double the risk of a recurrence of the infection compared to those aged under 65. Patients aged between 65-74 had 1.5 times the risk of recurrence compared to younger patients.

Prof. Leanord will conclude: “Having a clear understanding of the nature of C. difficile infections in Scotland will allow the Scottish government to target resources at the most appropriate patients to try to reduce the overall burden of the disease on the health service. Our findings are very likely to be applicable to the rest of the UK and other countries as well.”

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In a second presentation on Saturday, Dr David Enoch, a consultant microbiologist and infection control doctor at the National Infection Service, Public Health England, Cambridge (UK), will report the outcomes of 6,874 patients who had acquired C. difficile infection in hospital between 2002 and 2013 in England. Of these, 1,141 (16.6%) had recurrences of the infection.

“We found that 49% of hospital patients who suffer a recurrent episode of C. difficile infection die within a year, compared to 38% of those who suffer an initial infection only,” he will say. “In addition, 21% of patients with a recurrence suffered other complications as well, such as dehydration, malnourished and sometimes even perforation of the bowel, compared to 18% of patients who did not have a recurrence.”

Dr Enoch estimates that there are approximately 125,000 cases of C. difficile infection in Europe each year, and between 15-30% of these recur. “Cases in the UK have been coming down since 2008, which is most probably due to improvements in antibiotic prescribing and cleaning regimens in hospitals. This is encouraging but more still needs to be done.”

The average age of the patients was 77 and the average length of stay in hospital was 38 days.

“The main risk factor for developing C. difficile infection is prior antibiotic use. These patients are often already ill from some other underlying illness, which explains why they needed antibiotics in the first place. Older people are at greater risk of C. difficile infection as they are often sicker, have other illnesses or conditions, and so need more antibiotics,” he will say.

Dr Enoch continues: “Although much has been done, particularly in the UK, to try to prevent C. difficile infection, strict adherence to antibiotic guidelines by clinicians and thorough cleaning of the hospital environment are crucial in ensuring that patients don’t develop C. difficile infection in the first place. Treatment with a new drug called fidaxomicin has also been shown to reduce the risk of recurrence in patients who are unfortunate enough to develop an infection. However, we still have a lot to learn, particularly about how C. difficile infection occurs in the community, and how best to treat it.”

Treatments for recurrences of C. difficile infection  —–  include stopping the antibiotic that made the patient susceptible to the infection and starting a different antibiotic that is effective against C. difficile infection. These antibiotics include metronidazole, vancomycin and fidaxomicin. Supportive therapy, such as extra fluids, and surgery in serious or life-threatening cases may also be necessary. Faecal transplantation is emerging as a promising option; this is a process in which the good bacteria that the gut needs but which has been killed off by antibiotics is transplanted into the patient from a healthy donor.

(CDF:  Consider contacting an organization conducting Clinical Trials to Treat and Prevent.  Click on the following link for more information :  https://cdifffoundation.org/clinical-trials-2/

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Abstract no: #1672, presented by Prof. Alistair Leanord in the “Clostridium difficile infections: epidemiology and outcome” oral session, 16.30-18.30 hrs, Saturday 22 April, Hall A.

Abstract no: #883, presented by Dr Enoch in the “Clostridium difficile: guts and glory” e-poster mini-oral session, 15.30-16.30 hrs, Saturday 22 April, ePoster Arena 4.

 

To read the article in its entirety – please click on the following link:

https://www.eurekalert.org/pub_releases/2017-04/esoc-cdi041917.php