Population Council Projects | Clinical Studies: Carraguard® Phase 3 Efficacy Trial

PROJECT
Clinical Studies: Carraguard® Phase 3 Clinical Trial

The Phase 3 clinical trial of the Population Council’s candidate microbicide Carraguard was a milestone for microbicides development: it was the first Phase 3 trial of a novel candidate microbicide to be conducted among a general population of women and completed as planned without any safety concerns. (news release)

The trial did not show that Carraguard is effective in preventing HIV transmission during vaginal sex. Carraguard was found to be safe when used approximately once per week, on average, for up to two years, confirming results of previous safety trials. Carraguard’s favorable safety profile and physical properties make it a potentially useful vehicle for future microbicides.

Data collection on the trial began in March 2004 and was completed in March 2007 at three sites in South Africa: the University of Cape Town in Gugulethu; the University of Limpopo/Medunsa campus in Soshanguve, near Pretoria; and the Medical Research Council (MRC) in Isipingo, near Durban.

The primary objectives of the trial were to determine the efficacy of Carraguard gel in preventing male-to-female transmission of HIV when applied prior to vaginal sex, and to evaluate its safety when used for up to two years. A total of 6,202 women enrolled, with each woman participating in the trial for a minimum of nine months and a maximum of two years.

After a comprehensive informed consent process involving a study booklet and video made specifically for the Carraguard trial, eligible, consenting women were randomized to one of two groups: Carraguard gel plus condoms or its matching placebo (methyl cellulose) plus condoms. Neither participants nor study staff knew which participants had which gel. Women were instructed to insert the study gel before each act of vaginal intercourse and to come to the clinic for quarterly pelvic exams, interviews about sexual behavior, safer-sex counseling, testing and treatment of curable sexually transmitted infections, and free condoms. Women also were counseled to use a condom with each sex act.

During the trial, members of the Carraguard trial's Data Safety Monitoring Board, an independent group of scientists, reviewed the data three times to ensure participants' safety and did not recommend stopping the trial for any reason.

Vaginal applicators
Prior to the Carraguard trials, the Population Council conducted a pilot study in South Africa to assess the applicator that would be used in the trials.

Applicators were tracked by barcode.

Carraguard gel was distributed in pre-filled, single-dose, disposable, plastic Microlax® applicators (made by Norden Pac International AB, Kalmar, Sweden). The applicator had a small bulb that users pressed between the thumb and forefinger to squeeze the contents out through the elongated nozzle. Each applicator delivered approximately 4 ml of gel into the vagina. Results showed that the Microlax applicator performed well as a delivery system. In the same study, methyl cellulose gel was shown to be a safe placebo.

Location

Gugulethu, Isipingo, and Soshanguve, South Africa

Duration

March 2004–March 2007

Population Council researchers

Barbara Friedland, Marlena Gehret, Sumen Govender, Pekka O. Lähteenmäki, Robin A. Maguire

Non-Council collaborators

Khatija Ahmed (University of Limpopo/Medunsa campus)

Lydia Altini (University of Cape Town)

Gita Ramjee (South African Medical Research Council)

Donors

Bill & Melinda Gates Foundation

US Agency for International Development

Publications/Resources
Council researchers' names appear in boldface type.

2007
Ramjee, Gita, Neetha S. Morar, Sarah Braunstein, Barbara Friedland, Heidi Jones, and Janneke van de Wijgert. "Acceptability of Carraguard, a candidate microbicide and methyl cellulose placebo vaginal gels among HIV-positive women and men in Durban, South Africa," AIDS Research and Therapy 4: 20. (abstract)

van de Wijgert, Janneke H.H.M., Sarah Braunstein, Neetha S. Morar, Heidi Jones, Lorna Madurai, Tammy T. Evans Strickfaden, Manivasan Moodley, Jamila Aboobaker, Gugulethu Ndlovu, Taja M. Ferguson, Barbara A. Friedland, Clyde E. Hart, and Gita Ramjee. "Carraguard vaginal gel safety in HIV-positive women and men in South Africa," Journal of Acquired Immune Deficiency Syndromes 46(5): 538–546. (abstract)

2006
Skoler, Stephanie, Leigh Peterson, and Ward Cates. "Our current microbicide trials: Lessons learned and to be learned," Microbicide Quarterly 4(1): 1–6. (PDF)

2005
Skoler, Stephanie, Sumen Govender, Lydia Altini, Khatija Ahmed, Donald Waldron, Landon Myer, and Pekka Lähteenmäki. "Risks in the use of an unblinded control group (letter)," Journal of Infectious Diseases 191(8): 1378–1379.

van de Wijgert, Janneke, Heidi Jones, Annalie Pistorius, Alana de Kock, Mohlatlego Sebola, Barbara Friedland, Anwar Hoosen, and Nicol Coetzee. "Phase III microbicide trial methodology: Opinions of experienced expanded safety trial participants in South Africa," Journal of Social Aspects of HIV/AIDS 2(3): 311–319. (abstract) (résumé en français)

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