Devin Horton, MD

Clinical question: Is treatment with nontoxigenic C. diff strain M-3 (NTCD-M3) safe and effective in preventing recurrent Clostridium difficile infection (CDI)?

Background: C. diff is the most commonly identified healthcare pathogen, and CDI has a 25%-30% recurrence rate. Not all C. diff strains produce toxins, and gastrointestinal (GI) tract colonization with NTCD has been shown to prevent CDI when the patient is subsequently exposed to a toxigenic strain.

Study design: Multicenter, phase 2, randomized, double-blind, placebo-controlled, dose-ranging trial.

Setting: Forty-four centers in the U.S., Canada, and Europe.

Synopsis: Patients who had clinically recovered from CDI were randomized to placebo or NTCD-M3 at a dose of 104 spores/day for seven days, 107 spores/day for seven days, or 107 spores per day for 14 days. Patients were excluded who had multiple recurrences or other significant GI illnesses, were treated with antimicrobials other than metronidazole or PO [by mouth] vancomycin, had planned antibiotics, were unable to take PO, or had immunosuppression. Patients were monitored for side effects, rates of colonization, and incidence of CDI recurrence within six weeks.

Both overall and serious treatment-emergent adverse events were similar in patients receiving NTCD-M3 and those receiving placebo, but no statistical analysis was performed. Headache was more common in treatment groups.

CDI recurrence occurred in 31% of placebo patients and 11% of patients who received NTCD-M3 (OR 0.28). Fecal colonization was achieved in 69% of NTCD-M3 patients; this subset of patients had a 2% recurrence. Patients who received NTDC but did not achieve GI colonization had rates of recurrent CDI similar to placebo.

Bottom line: Use of NTCD-M3 spores appears safe and well tolerated and led to decreased recurrent CDI, primarily in patients who achieved fecal colonization.

Citation: Gerding DN, Meyer T, Lee C, et al. Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial. JAMA. 2015;313(17):1719-1727.

Clinical question: Is treatment with nontoxigenic C. diff strain M-3 (NTCD-M3) safe and effective in preventing recurrent Clostridium difficile infection (CDI)?

Background: C. diff is the most commonly identified healthcare pathogen, and CDI has a 25%-30% recurrence rate. Not all C. diff strains produce toxins, and gastrointestinal (GI) tract colonization with NTCD has been shown to prevent CDI when the patient is subsequently exposed to a toxigenic strain.

Study design: Multicenter, phase 2, randomized, double-blind, placebo-controlled, dose-ranging trial.

Setting: Forty-four centers in the U.S., Canada, and Europe.

Synopsis: Patients who had clinically recovered from CDI were randomized to placebo or NTCD-M3 at a dose of 104 spores/day for seven days, 107 spores/day for seven days, or 107 spores per day for 14 days. Patients were excluded who had multiple recurrences or other significant GI illnesses, were treated with antimicrobials other than metronidazole or PO [by mouth] vancomycin, had planned antibiotics, were unable to take PO, or had immunosuppression. Patients were monitored for side effects, rates of colonization, and incidence of CDI recurrence within six weeks.

Both overall and serious treatment-emergent adverse events were similar in patients receiving NTCD-M3 and those receiving placebo, but no statistical analysis was performed. Headache was more common in treatment groups.

CDI recurrence occurred in 31% of placebo patients and 11% of patients who received NTCD-M3 (OR 0.28). Fecal colonization was achieved in 69% of NTCD-M3 patients; this subset of patients had a 2% recurrence. Patients who received NTDC but did not achieve GI colonization had rates of recurrent CDI similar to placebo.

Bottom line: Use of NTCD-M3 spores appears safe and well tolerated and led to decreased recurrent CDI, primarily in patients who achieved fecal colonization.

Citation: Gerding DN, Meyer T, Lee C, et al. Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial. JAMA. 2015;313(17):1719-1727.

Clinical question: Is treatment with nontoxigenic C. diff strain M-3 (NTCD-M3) safe and effective in preventing recurrent Clostridium difficile infection (CDI)?

Background: C. diff is the most commonly identified healthcare pathogen, and CDI has a 25%-30% recurrence rate. Not all C. diff strains produce toxins, and gastrointestinal (GI) tract colonization with NTCD has been shown to prevent CDI when the patient is subsequently exposed to a toxigenic strain.

Study design: Multicenter, phase 2, randomized, double-blind, placebo-controlled, dose-ranging trial.

Setting: Forty-four centers in the U.S., Canada, and Europe.

Synopsis: Patients who had clinically recovered from CDI were randomized to placebo or NTCD-M3 at a dose of 104 spores/day for seven days, 107 spores/day for seven days, or 107 spores per day for 14 days. Patients were excluded who had multiple recurrences or other significant GI illnesses, were treated with antimicrobials other than metronidazole or PO [by mouth] vancomycin, had planned antibiotics, were unable to take PO, or had immunosuppression. Patients were monitored for side effects, rates of colonization, and incidence of CDI recurrence within six weeks.

Both overall and serious treatment-emergent adverse events were similar in patients receiving NTCD-M3 and those receiving placebo, but no statistical analysis was performed. Headache was more common in treatment groups.

CDI recurrence occurred in 31% of placebo patients and 11% of patients who received NTCD-M3 (OR 0.28). Fecal colonization was achieved in 69% of NTCD-M3 patients; this subset of patients had a 2% recurrence. Patients who received NTDC but did not achieve GI colonization had rates of recurrent CDI similar to placebo.

Bottom line: Use of NTCD-M3 spores appears safe and well tolerated and led to decreased recurrent CDI, primarily in patients who achieved fecal colonization.

Citation: Gerding DN, Meyer T, Lee C, et al. Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial. JAMA. 2015;313(17):1719-1727.

Clinical question: Does a retrievable inferior vena cava (IVC) filter in addition to anticoagulation in patients with an acute pulmonary embolism (PE) decrease the risk of recurrent PE?

Background: Inferior vena cava placement has increased dramatically over the last three decades. Although IVC filter placement benefits patients with a contraindication to anticoagulation, the benefit of a temporary IVC filter in addition to anticoagulation to prevent PE in patients at high risk of recurrence is unknown.

Study design: Randomized, open-label.

Setting: Seventeen French hospitals.

Synopsis: Nearly 400 patients with an acute PE associated with lower extremity thrombosis and at least one additional risk factor for severity were randomized to anticoagulation in combination with a retrievable IVC filter versus anticoagulation alone. Risk factors included age, active cancer, chronic cardiac or respiratory disease, recent ischemic stroke with leg paralysis, bilateral deep vein thrombosis, or right ventricular failure or myocardial injury. Both groups received anticoagulation for six months.

Overall, there was no difference in fatal or symptomatic nonfatal PE in each group at three and six months.

The open-label design is subject to interpretative bias. A blinded outcome assessment committee and a central randomization process were implemented in order to minimize bias. In addition, the study could have been underpowered given the limited number of patients and low PE recurrence rate.

Bottom line: In patients with an acute PE at high risk of recurrent PE, retrievable IVC filter in addition to standard anticoagulation therapy does not decrease the risk of recurrence.

Citation: Mismetti, P, Laporte, S, Pellerin O, et al. Effect of a retrievable inferior vena cava filter plus anticoagulation vs anticoagulation alone on risk of recurrent pulmonary embolism. JAMA. 2015;313(16):1627-1635.

Clinical question: Does a retrievable inferior vena cava (IVC) filter in addition to anticoagulation in patients with an acute pulmonary embolism (PE) decrease the risk of recurrent PE?

Background: Inferior vena cava placement has increased dramatically over the last three decades. Although IVC filter placement benefits patients with a contraindication to anticoagulation, the benefit of a temporary IVC filter in addition to anticoagulation to prevent PE in patients at high risk of recurrence is unknown.

Study design: Randomized, open-label.

Setting: Seventeen French hospitals.

Synopsis: Nearly 400 patients with an acute PE associated with lower extremity thrombosis and at least one additional risk factor for severity were randomized to anticoagulation in combination with a retrievable IVC filter versus anticoagulation alone. Risk factors included age, active cancer, chronic cardiac or respiratory disease, recent ischemic stroke with leg paralysis, bilateral deep vein thrombosis, or right ventricular failure or myocardial injury. Both groups received anticoagulation for six months.

Overall, there was no difference in fatal or symptomatic nonfatal PE in each group at three and six months.

The open-label design is subject to interpretative bias. A blinded outcome assessment committee and a central randomization process were implemented in order to minimize bias. In addition, the study could have been underpowered given the limited number of patients and low PE recurrence rate.

Bottom line: In patients with an acute PE at high risk of recurrent PE, retrievable IVC filter in addition to standard anticoagulation therapy does not decrease the risk of recurrence.

Citation: Mismetti, P, Laporte, S, Pellerin O, et al. Effect of a retrievable inferior vena cava filter plus anticoagulation vs anticoagulation alone on risk of recurrent pulmonary embolism. JAMA. 2015;313(16):1627-1635.

Clinical question: Does a retrievable inferior vena cava (IVC) filter in addition to anticoagulation in patients with an acute pulmonary embolism (PE) decrease the risk of recurrent PE?

Background: Inferior vena cava placement has increased dramatically over the last three decades. Although IVC filter placement benefits patients with a contraindication to anticoagulation, the benefit of a temporary IVC filter in addition to anticoagulation to prevent PE in patients at high risk of recurrence is unknown.

Study design: Randomized, open-label.

Setting: Seventeen French hospitals.

Synopsis: Nearly 400 patients with an acute PE associated with lower extremity thrombosis and at least one additional risk factor for severity were randomized to anticoagulation in combination with a retrievable IVC filter versus anticoagulation alone. Risk factors included age, active cancer, chronic cardiac or respiratory disease, recent ischemic stroke with leg paralysis, bilateral deep vein thrombosis, or right ventricular failure or myocardial injury. Both groups received anticoagulation for six months.

Overall, there was no difference in fatal or symptomatic nonfatal PE in each group at three and six months.

The open-label design is subject to interpretative bias. A blinded outcome assessment committee and a central randomization process were implemented in order to minimize bias. In addition, the study could have been underpowered given the limited number of patients and low PE recurrence rate.

Bottom line: In patients with an acute PE at high risk of recurrent PE, retrievable IVC filter in addition to standard anticoagulation therapy does not decrease the risk of recurrence.

Citation: Mismetti, P, Laporte, S, Pellerin O, et al. Effect of a retrievable inferior vena cava filter plus anticoagulation vs anticoagulation alone on risk of recurrent pulmonary embolism. JAMA. 2015;313(16):1627-1635.