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Three months weekly Rifapentine plus Isoniazid in the treatment of latent TB infection

A study of the effectiveness and tolerability of weekly Rifapentine/Isoniazid for three months versus daily isoniazid for nine months for the treatment of latent tuberculosis infection.

This study will evaluate the effectiveness and tolerability of a novel regimen for preventing TB in people at high risk of developing the active form of tuberculosis (TB disease). A person who is HIV positive is considered at "high risk" of developing TB if he/she is in close contact with others who have active TB or if he/she has received a tuberculin skin test (TST) that indicates the presence of TB germs in the body (TB infection).

The novel regimen consists of rifapentine (RPT) plus isoniazid (INH) and is given once weekly for a duration of three months (3RPT/INH). It will be compared to the standard nine-month daily regimen of INH alone (9INH).

Study participants will be followed for two years after completing therapy for evidence of active TB. For 21 months, there will be follow-up every three months. Thereafter, follow-up will occur every six months until the end of the two-year study period. After the trial has ended, National US and Canadian TB databases will be used for long-term follow-up.

Drug toxicity of both regimens will be compared as will completion and discontinuation rates of study therapy due to bad drug reaction and for any other reason associated with treatment. Participants who discontinue study therapy due to RPT toxicity can switch to the 9INH group. The study doctor(s) will decide what treatment to use should participants discontinue their INH treatment due to toxicity. Among participants who are also receiving methadone, rates of withdrawal from methadone that are associated with both treatments will be evaluated. Patterns of the TB disease's resistance to treatment in participants who develop TB disease in spite of therapy will also be monitored.

Participants will be randomly assigned to one of the following treatment groups:

3RPT/INH Group (under supervision of study doctor/nurse): 900 mg RPT (750 mg RPT if participant weighs under 50 kg) once a week x 12 doses over three months + 15 mg INH/kg of person's weight once a week x 12 doses over three months
9INH Group (self-administered or under supervision of doctor/nurse): 5 mg INH/kg of person's weight daily x 270 doses over nine months

It is recommended that 50 mg of pyridoxine (vitamin B6) be given with each dose of isoniazid in both groups to reduce the risk of INH toxicity.

This international trial anticipates a total enrolment of 8000 participants over the next three years. The Canadian site is hoping to enroll 70 participants.

Tuberculosis (TB) is an infection that may occur in individuals infected with HIV. It is an opportunistic infection (OI) in the lungs caused by Mycobacterium tuberculosis. TB infection is contracted through close contact with someone who has active untreated TB germs in their lungs and throat. In most cases, the immune system (the body's natural defense system) contains the mycobacteria by building a wall around the germs where they become latent (inactive). When the body's defenses are weak due to aging, a serious illness, drug/alcohol abuse, or HIV infection, the germs can break out of the walls, multiply and cause damage to lungs or other organs. These active germs cause active TB disease.

The recommended therapy for latent tuberculosis (TB) consists of isoniazid (INH) once daily for a period of 6 to 12 months. The frequency with which medication must be taken and particularly the difficulty experienced by some people in adhering to the full length of treatment limit the usefulness of this standard therapy. If not taken as prescribed, the treatment leads to the development of resistant tuberculosis (the bacteria are no longer sensitive to the drug). There is therefore a need for alternative therapies.

Rifapentine (RPT/Priftin) and isoniazid (INH) are both antibiotic agents. Antibiotics are drugs used to kill or harm specific bacteria such as tuberculosis (TB). Rifapentine is not licensed in Canada but is licensed in the USA.

Pryridoxine (vitamin B6) is used by the body to maintain proper function of the central nervous system. Since isoniazid (INH) binds to and deactivates pryridoxine in the body, it is recommended that pryridoxine be taken as a supplement to INH treatment.

Closed to enrolment

Vancouver General Hospital, Vancouver, BC
Investigator: Dr. Mark Fitzgerald
Information: 604-875-4565

University of Manitoba, Winnipeg, MB
Investigator: Dr. Earl Hershfield
Information: 204-787-2977

Montreal Chest Institute McGill University, Montreal, QC
Investigator: Dr. Richard I. Menzies
Information: 514-398-8122

Required
	Be 12 years of age or older
	Be at high risk for developing TB but without evidence of active TB (High risk includes: people who have converted from a negative to a positive tuberculin skin test [TST] within a two-year period, TST-positive close contacts of people with active TB [as part of a contact investigation], HIV-positive people who are also TST positive or who are in close contact with others who have active TB, people who are TST positive with no prior history of TB treatment and do not have active TB but who have clinically significant [determined by study doctor] scarring of the lungs as determined by chest X-ray[s])
	Be willing to provide signed informed consent, or parental consent and participant assent
Not Allowed
	Pregnancy or breastfeeding
	Use of protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the first 90 days following enrolment
	Culture-confirmed TB or suspected TB as judged by study doctor(s)
	TB that is resistant to the antibiotics isoniazid or rifampin
	History of sensitivity or intolerance to isoniazid or rifamycins
	Treatment in the last two years with the antibiotic rifamycin for more than 14 consecutive days or with INH for more than 30 consecutive days
	Use of the antibiotics rifabutin, rifampin or pyrazinamide during the study and follow-up phase
Note: Other criteria may apply.




Canadian AIDS Treatment Information Exchange
This information is provided in collaboration with CATIE. For information on the benefits and risks of participating in HIV clinical trials, call CATIE toll-free at 1-800-263-1638.