Michael Smith : May 19, 2011
DENVER -- Two rifamycin derivatives had equal efficacy against pulmonary tuberculosis in an international, phase II trial, a researcher said here.
Rifapentine (Priftin) and rifampin (Rifadin, Rimactane) showed equal activity when they were added to standard therapy during the first eight weeks of treatment, according to Susan Dorman, MD, of Johns Hopkins University.
But the result was surprising because animal studies had suggested that rifapentine would be markedly better, Dorman said in a late-breaking abstract session at the annual meeting of the American Thoracic Society.
The rifamycin derivatives are "key sterilizing components of current standard treatment for active TB," Dorman said. Of those drugs, rifampin is the most widely used, but it may not be the best, she added.
In particular, less rifapentine is needed to inhibit a given amount of Mycobacterium tuberculosis, and it lasts longer in the body than rifampin, she said.
Studies in mice showed that treatment with rifapentine cured TB in three months compared with six months for rifampin, Dorman added. "There is a need for shorter regimens" in humans, she noted.
To test the compound in humans, she and colleagues added either it or rifampin to standard early therapy -- isoniazid (Nydrazid, Tubizid), pyrazinamide, and ethambutol (Myambutol) -- five days a week for eight weeks.
The goal was see if there were differences in the proportion of patients with negative sputum cultures at the end of the intensive phase of treatment, Dorman said.
The researchers also evaluated safety and tolerability, she said.
All told, 531 patients took part, almost half of them in Africa; 255 were assigned to the rifampin arm and 276 to rifapentine. About 70 participants in each arm were either lost to follow up or were found not to be eligible, Dorman reported.
The researchers had expected to see a 15% difference in the rate of culture negativity, Dorman said, but instead the difference was about 3%.
Specifically:
When the sputum samples were analyzed in liquid media, 71.5% of rifampin patients and 75.3% of rifapentine patients had negative cultures after eight weeks.
In solid media, the proportions were 88.9% and 91.9%, respectively.
Neither difference was statistically significant.
Both drugs appeared equally safe and tolerable, Dorman reported.
In the rifampin arm, 15.7% of patients stopped therapy, compared with 14.5% of the rifapentine patients, she said. The rates of adverse events were also similar -- 18.1% for rifampin versus 22.6% for rifapentine -- and 2.8% of rifampin patients reported hepatitis compared with 3.6% of rifapentine patients.
It remains unclear why the expected difference did not materialize, Dorman said, adding that it could be a function of dosing levels or perhaps the fact that both drugs were taken without food.
She noted that the proportion of culture conversions is a surrogate marker for the sterilizing activity of the drugs which may not have been a good reflection of that activity.
The study was supported by the CDC. Study drugs were donated by sanofi-aventis. Dorman said she had no conflicts.
Source reference: Dorman S, et al "A phase II study of a rifapentine-containing regimen for intensive phase treatment of pulmonary tuberculosis: Preliminary results for tuberculosis trials consortium study 29" Am J Respir Crit Care Med 2011; 183: A6413.
http://www.medpagetoday.com/MeetingCoverage/ATS/26575
DENVER -- Two rifamycin derivatives had equal efficacy against pulmonary tuberculosis in an international, phase II trial, a researcher said here.
Rifapentine (Priftin) and rifampin (Rifadin, Rimactane) showed equal activity when they were added to standard therapy during the first eight weeks of treatment, according to Susan Dorman, MD, of Johns Hopkins University.
But the result was surprising because animal studies had suggested that rifapentine would be markedly better, Dorman said in a late-breaking abstract session at the annual meeting of the American Thoracic Society.
The rifamycin derivatives are "key sterilizing components of current standard treatment for active TB," Dorman said. Of those drugs, rifampin is the most widely used, but it may not be the best, she added.
In particular, less rifapentine is needed to inhibit a given amount of Mycobacterium tuberculosis, and it lasts longer in the body than rifampin, she said.
Studies in mice showed that treatment with rifapentine cured TB in three months compared with six months for rifampin, Dorman added. "There is a need for shorter regimens" in humans, she noted.
To test the compound in humans, she and colleagues added either it or rifampin to standard early therapy -- isoniazid (Nydrazid, Tubizid), pyrazinamide, and ethambutol (Myambutol) -- five days a week for eight weeks.
The goal was see if there were differences in the proportion of patients with negative sputum cultures at the end of the intensive phase of treatment, Dorman said.
The researchers also evaluated safety and tolerability, she said.
All told, 531 patients took part, almost half of them in Africa; 255 were assigned to the rifampin arm and 276 to rifapentine. About 70 participants in each arm were either lost to follow up or were found not to be eligible, Dorman reported.
The researchers had expected to see a 15% difference in the rate of culture negativity, Dorman said, but instead the difference was about 3%.
Specifically:
When the sputum samples were analyzed in liquid media, 71.5% of rifampin patients and 75.3% of rifapentine patients had negative cultures after eight weeks.
In solid media, the proportions were 88.9% and 91.9%, respectively.
Neither difference was statistically significant.
Both drugs appeared equally safe and tolerable, Dorman reported.
In the rifampin arm, 15.7% of patients stopped therapy, compared with 14.5% of the rifapentine patients, she said. The rates of adverse events were also similar -- 18.1% for rifampin versus 22.6% for rifapentine -- and 2.8% of rifampin patients reported hepatitis compared with 3.6% of rifapentine patients.
It remains unclear why the expected difference did not materialize, Dorman said, adding that it could be a function of dosing levels or perhaps the fact that both drugs were taken without food.
She noted that the proportion of culture conversions is a surrogate marker for the sterilizing activity of the drugs which may not have been a good reflection of that activity.
The study was supported by the CDC. Study drugs were donated by sanofi-aventis. Dorman said she had no conflicts.
Source reference: Dorman S, et al "A phase II study of a rifapentine-containing regimen for intensive phase treatment of pulmonary tuberculosis: Preliminary results for tuberculosis trials consortium study 29" Am J Respir Crit Care Med 2011; 183: A6413.
http://www.medpagetoday.com/MeetingCoverage/ATS/26575
