Frozen noninferior to fresh fecal microbiota transplantation

Fecal microbiota transplantation using frozen-then-thawed fecal material proved noninferior to that using fresh material for treating recurrent or refractory Clostridium difficile infection, according to a report published online Jan. 12 in JAMA.

Using frozen rather than fresh fecal material offers many advantages, such as allowing much more widespread and immediate accessibility of the treatment; reducing the number and frequency of donor screenings, which in turn would reduce costs; and ameliorating concern about potential transmission of pathogens from the donor to the recipient, since samples could be stored in quarantine until screening results are known, said Dr. Christine H. Lee of the department of pathology and molecular medicine, McMaster University, Hamilton (Ont.), and her associates.

CDC/D. Holdeman

They performed a 2-year randomized, double-blind noninferiority trial at six academic medical centers in Canada to compare frozen with fresh donor material in 232 adults with recurrent or refractory C. difficile infection. These study participants had “an extensive burden of comorbidity”: most had inflammatory bowel diseases and approximately 85% were immunocompromised, having undergone chronic hemodialysis or kidney transplantation, or having had metastatic solid tumors or hematologic malignancies. Half of the study subjects were inpatients, and approximately 75% were aged 65 years and older.

The patients were assigned to receive 50 mL of frozen-then-thawed FMT (114 participants) or fresh FMT (118 participants) by retention enema, delivered using 60-mL syringes. Those who didn’t improve by day 4 were given an additional FMT from the same donor. “Administration by enema is significantly less invasive than colonoscopy or nasojejunal/gastric administration and can be performed outside an acute care facility,” Dr. Lee and her associates noted.

The primary efficacy endpoint was clinical resolution, defined as no recurrence of C. difficile–related diarrhea at 13 weeks and no need for antibiotics. In the per-protocol population, 83.5% of the frozen FMT group and 85.1% of the fresh FMT group achieved this endpoint. In the intention-to-treat population, 75.0% of the frozen FMT group and 70.3% of the fresh FMT group achieved it. Both results demonstrate the noninferiority of frozen FMT, the investigators said (JAMA. 2016;315[2]:142-9. doi:10.1001/jama.201518098).

The proportion of adverse events and severe adverse events was deemed low and did not differ between the two study groups. The most common adverse events that may possibly have been related to treatment occurred in similar numbers of each group and included transient diarrhea, abdominal cramps, and nausea during the first 24 hours after transplantation and constipation and excess flatulence during the 13-week follow-up.

Even though this follow-up was longer than that in most clinical trials of FMT for C. difficile infection, which only tracked patients for 40 days, it is still insufficient to assess the long-term safety of the treatment. Ten-year follow-up of the participants in this trial is currently under way to examine any beneficial effects the treatment might exert on the metabolic syndrome, diabetes, or autoimmune disease, as well as any negative effects such as the development of autoimmune disorders or cancer.

Fecal microbiota transplantation using frozen-then-thawed fecal material proved noninferior to that using fresh material for treating recurrent or refractory Clostridium difficile infection, according to a report published online Jan. 12 in JAMA.

Using frozen rather than fresh fecal material offers many advantages, such as allowing much more widespread and immediate accessibility of the treatment; reducing the number and frequency of donor screenings, which in turn would reduce costs; and ameliorating concern about potential transmission of pathogens from the donor to the recipient, since samples could be stored in quarantine until screening results are known, said Dr. Christine H. Lee of the department of pathology and molecular medicine, McMaster University, Hamilton (Ont.), and her associates.

CDC/D. Holdeman

They performed a 2-year randomized, double-blind noninferiority trial at six academic medical centers in Canada to compare frozen with fresh donor material in 232 adults with recurrent or refractory C. difficile infection. These study participants had “an extensive burden of comorbidity”: most had inflammatory bowel diseases and approximately 85% were immunocompromised, having undergone chronic hemodialysis or kidney transplantation, or having had metastatic solid tumors or hematologic malignancies. Half of the study subjects were inpatients, and approximately 75% were aged 65 years and older.

The patients were assigned to receive 50 mL of frozen-then-thawed FMT (114 participants) or fresh FMT (118 participants) by retention enema, delivered using 60-mL syringes. Those who didn’t improve by day 4 were given an additional FMT from the same donor. “Administration by enema is significantly less invasive than colonoscopy or nasojejunal/gastric administration and can be performed outside an acute care facility,” Dr. Lee and her associates noted.

The primary efficacy endpoint was clinical resolution, defined as no recurrence of C. difficile–related diarrhea at 13 weeks and no need for antibiotics. In the per-protocol population, 83.5% of the frozen FMT group and 85.1% of the fresh FMT group achieved this endpoint. In the intention-to-treat population, 75.0% of the frozen FMT group and 70.3% of the fresh FMT group achieved it. Both results demonstrate the noninferiority of frozen FMT, the investigators said (JAMA. 2016;315[2]:142-9. doi:10.1001/jama.201518098).

The proportion of adverse events and severe adverse events was deemed low and did not differ between the two study groups. The most common adverse events that may possibly have been related to treatment occurred in similar numbers of each group and included transient diarrhea, abdominal cramps, and nausea during the first 24 hours after transplantation and constipation and excess flatulence during the 13-week follow-up.

Even though this follow-up was longer than that in most clinical trials of FMT for C. difficile infection, which only tracked patients for 40 days, it is still insufficient to assess the long-term safety of the treatment. Ten-year follow-up of the participants in this trial is currently under way to examine any beneficial effects the treatment might exert on the metabolic syndrome, diabetes, or autoimmune disease, as well as any negative effects such as the development of autoimmune disorders or cancer.

Fecal microbiota transplantation using frozen-then-thawed fecal material proved noninferior to that using fresh material for treating recurrent or refractory Clostridium difficile infection, according to a report published online Jan. 12 in JAMA.

Using frozen rather than fresh fecal material offers many advantages, such as allowing much more widespread and immediate accessibility of the treatment; reducing the number and frequency of donor screenings, which in turn would reduce costs; and ameliorating concern about potential transmission of pathogens from the donor to the recipient, since samples could be stored in quarantine until screening results are known, said Dr. Christine H. Lee of the department of pathology and molecular medicine, McMaster University, Hamilton (Ont.), and her associates.

CDC/D. Holdeman

They performed a 2-year randomized, double-blind noninferiority trial at six academic medical centers in Canada to compare frozen with fresh donor material in 232 adults with recurrent or refractory C. difficile infection. These study participants had “an extensive burden of comorbidity”: most had inflammatory bowel diseases and approximately 85% were immunocompromised, having undergone chronic hemodialysis or kidney transplantation, or having had metastatic solid tumors or hematologic malignancies. Half of the study subjects were inpatients, and approximately 75% were aged 65 years and older.

The patients were assigned to receive 50 mL of frozen-then-thawed FMT (114 participants) or fresh FMT (118 participants) by retention enema, delivered using 60-mL syringes. Those who didn’t improve by day 4 were given an additional FMT from the same donor. “Administration by enema is significantly less invasive than colonoscopy or nasojejunal/gastric administration and can be performed outside an acute care facility,” Dr. Lee and her associates noted.

The primary efficacy endpoint was clinical resolution, defined as no recurrence of C. difficile–related diarrhea at 13 weeks and no need for antibiotics. In the per-protocol population, 83.5% of the frozen FMT group and 85.1% of the fresh FMT group achieved this endpoint. In the intention-to-treat population, 75.0% of the frozen FMT group and 70.3% of the fresh FMT group achieved it. Both results demonstrate the noninferiority of frozen FMT, the investigators said (JAMA. 2016;315[2]:142-9. doi:10.1001/jama.201518098).

The proportion of adverse events and severe adverse events was deemed low and did not differ between the two study groups. The most common adverse events that may possibly have been related to treatment occurred in similar numbers of each group and included transient diarrhea, abdominal cramps, and nausea during the first 24 hours after transplantation and constipation and excess flatulence during the 13-week follow-up.

Even though this follow-up was longer than that in most clinical trials of FMT for C. difficile infection, which only tracked patients for 40 days, it is still insufficient to assess the long-term safety of the treatment. Ten-year follow-up of the participants in this trial is currently under way to examine any beneficial effects the treatment might exert on the metabolic syndrome, diabetes, or autoimmune disease, as well as any negative effects such as the development of autoimmune disorders or cancer.