Terri Walsh

Randomised controlled trial of prophylactic antibiotics before insertion of intrauterine devices

Summary Background The value of antibiotic prophylaxis before insertion of an intrauterine device (IUD) remains uncertain. We undertook a triple-masked, randomised, placebo-controlled trial to find out whether such prophylaxis reduces the rate of IUD removal within 90 days. Methods 11 clinic sites in southern California enrolled women who requested IUD insertion and were at low risk of sexually transmitted infection according to self-reported medical history. We randomly assigned 1985 participants either 500 mg azithromycin or placebo capsules of identical appearance taken about 1 h before insertion of a Copper T 380A IUD. 118 women did not have an IUD inserted. We followed up 1833 of the remaining 1867 (98%) participants for at least 90 days after insertion. Findings The rate of IUD removal for any reason other than partial expulsion was 3·8% (35/918) in the antibiotic group and 3·4% (31/915) in the placebo group (relative risk 1·1 [95% Cl 0·7–1·8]). The two treatment groups sought medical attention with equal frequency (mean 38 visits per 100 women). During the 90 days after IUD insertion, only one woman from each assignment group had salpingitis, as defined by established criteria. Interpretation Prophylaxis with azithromycin did not affect the likelihood that a woman would retain her IUD at 90 days or the frequency of postinsertion medical attention. In appropriately screened women, the risk of upper-genitaltract infection is negligible after IUD insertion, with or without the administration of prophylactic antibiotics.

Evaluation of the efficacy of a nonlatex condom: results from a randomized, controlled clinical trial.

CONTEXT To reduce unintended pregnancy and HIV infection, it is critical to develop reliable male condoms that will attract consumers who reject conventional latex condoms. METHODS In a prospective clinical trial conducted in 1998-2000, 830 monogamous couples were randomized in equal numbers to use either a nonlatex condom or a commercial natural latex condom for six months as their only method of birth control. Couples completed detailed reports for the first five condom uses and recorded intercourse and condom use in coital diaries. Pregnancy rates associated with typical and consistent condom use were calculated using life-table analysis. Rates of clinical failure (condom breakage or slippage) were determined for the first five condom uses. RESULTS During the first five uses, the nonlatex condom had a higher frequency of breakage or slippage during intercourse or withdrawal (4.0%) than latex condoms (1.3%); the breakage rate for the nonlatex condom was about eight times that of latex condoms. The six-cycle typical-use pregnancy rate did not differ significantly between users of nonlatex (10.8%) and latex condoms (6.4%). The six-cycle consistent-use pregnancy rate was higher for nonlatex condom users than for latex condom users (4.9% vs. 1.0%). CONCLUSIONS The data present strong indirect support for public health messages that promote the use of latex condoms and, for individuals who cannot or are unwilling to use latex condoms, the use of nonlatex condoms for prevention of pregnancy and disease.

Cellulose sulfate: tolerance and acceptability of penile application.

Sodium cellulose sulfate (CS) is under development as a vaginal microbicide and spermicide. This was a Phase I, randomized, double-blind study of men to assess acceptability, safety, and degree of penile irritation of seven consecutive daily doses of CS compared to an active control containing nonoxynol-9 (Conceptrol). The data suggest that CS gel is not more irritating to the male genitalia than Conceptrol. This, along with the minimal irritation seen in a Phase I safety study in women following 6 consecutive days of vaginal administration, suggests that CS could be used in future studies, without undue risk, where couples engage in vaginal intercourse. Male volunteers in future studies should be informed that 1 out of 24 participants in the CS group in this study experienced tingling and slight stinging for a brief time after exposure compared with 3 out of 12 in the Conceptrol group who reported similar symptoms.

Breakage and acceptability of a polyurethane condom: a randomized, controlled study.

CONTEXT Although the first commercial polyurethane condom was approved for use several years ago, no U.S. clinical trial has compared its performance to that of the latex condom. METHODS In a masked crossover study, 360 couples were randomized to use three polyurethane condoms and three latex condoms. After each use, couples recorded condom breaks, condom slips and other aspects of performance. At completion of the study, couples compared the sensitivity, ease of use, fit and lubrication of the two types of condoms. RESULTS The clinical breakage rate of the polyurethane condom was 7.2%, compared with 1.1% for the latex condom (relative risk of 6.6, 95% confidence interval of 3.5-12.3). The complete slippage rate (combining incidents during intercourse and withdrawal) of the polyurethane condom was 3.6%, compared with 0.6% for the latex condom (relative risk of 6.0, 95% confidence interval of 2.6-14.2). Most male users preferred the sensitivity provided by the polyurethane condom to that of the latex condom. CONCLUSIONS The clinical breakage rate of the polyurethane condom is significantly higher than that of the latex condom. However, nearly half of the users preferred the polyurethane condom, which provides an option for couples who have rejected conventional condoms or who cannot use latex products.

Safety and acceptability of penile application of 2 candidate topical microbicides: BufferGel and PRO 2000 Gel: 3 randomized trials in healthy low-risk men and HIV-positive men.

Objectives: To assess safety and acceptability of penile application of BufferGel (ReProtect, Baltimore, MD) and PRO 2000 Gel (Indevus Pharmaceuticals, Lexington, MA)compared with placebo among low‐risk sexually abstinent men and HIV‐positive sexually abstinent men. Design: Seventy‐two healthy low‐risk men (36 uncircumcised) and 25 HIV‐positive men (12 uncircumcised) were enrolled in 3 double‐blind, single‐center studies as follows: 36 low‐risk men in a study of BufferGel and K‐Y Jelly (McNeil‐PPC, Skillman, NJ) placebo; 36 low‐risk men in a study of PRO 2000 Gel and vehicle placebo; and 25 HIV‐positive men in a crossover study of BufferGel, PRO 2000 Gel, and K‐Y Jelly placebo. Methods: Participants applied product to the penis on 7 consecutive nights, kept study diaries, and were then interviewed and examined. Urine was tested for inflammation by leukocyte esterase. Results: No serious adverse events (AEs) or urethral inflammation was detected. During use of BufferGel, 3 low‐risk men (13%) reported 6 AEs and 2 HIV‐positive men (8%) reported 3 AEs. During use of PRO 2000 Gel, 4 low‐risk men (17%) reported 6 AEs and 1 HIV‐positive participant (4%) had 1 AE. AE rates during use of BufferGel and PRO 2000 Gel use were not significantly different from rates observed during placebo. One low‐risk man (4%) would object to his partners using BufferGel and 3 (13%) to PRO 2000 Gel. Two HIV‐positive men (8%) reported they would object to partners using either BufferGel or PRO 2000 Gel. Conclusions: Daily application of BufferGel and PRO 2000 Gel directly to the penis consecutively for 7 days was generally safe and well tolerated among healthy low‐risk men and HIV‐positive men. These microbicides have acceptable safety profiles to proceed with planned phase 3 vaginal microbicide trials.

Use of prostate-specific antigen (PSA) to measure semen exposure resulting from male condom failures: implications for contraceptive efficacy and the prevention of sexually transmitted disease

Accurate measurement of semen exposure resulting from condom failures can refine public health messages and improve predictions of condom efficacy in preventing pregnancy and HIV transmission. Eight hundred and thirty couples enrolled in a condom efficacy study were asked to collect a baseline sample of ejaculate from the inside of the first study condom they used and to collect a postcoital vaginal sample whenever a study condom broke or slipped off during intercourse. All samples were quantitatively tested for prostate-specific antigen (PSA), a substance found only in human semen, using rocket immunoelectrophoresis, and inspected microscopically for presence of sperm. Sixty-eight baseline ejaculate samples collected from the inside of the first study condom by couples who subsequently experienced a condom failure averaged 13.4 microg PSA per swab and 79% of the samples averaged one or more sperm per high power field (hpf). Seventy-nine postcoital vaginal samples obtained after a condom break averaged 5.7 microg PSA per swab and only 38% averaged one or more sperm per hpf. The PSA results indicated a 50% reduction in semen exposure compared to baseline levels (p = 0.0001). Seventeen samples obtained after a condom slip-off averaged 2.5 microg PSA per swab and none of the samples averaged one or more sperm per hpf. The PSA results indicated an 80% reduction in semen exposure compared to baseline levels (p = 0.0001). Our results suggest that even condoms that fail reduce the risk of pregnancy and the transmission of sexually transmitted disease compared to unprotected intercourse. We also used PSA results to adjust a model designed to predict consistent-use pregnancy rates from condom breakage and slippage data.

Comparative evaluation of three TactylonTM condoms and a latex condom during vaginal intercourse: breakage and slippage

This study compared breakage and slippage rates of three male condom styles made of Tactylon(TM), a synthetic elastomer, to those of a marketed latex condom during vaginal intercourse. Safety and acceptability outcomes were also assessed. This two-center, prospective, crossover study enrolled 443 couples. Each couple was randomly assigned to use three condoms of each type in one of 24 use sequences. Couples completed questionnaires after using each condom, all of one condom type, and all four condom types. The percentage and standard error (SE, in parentheses) of latex condoms with clinical breakage was 0.86% (0.295). Percentages for Tactylon condoms were not equivalent to the latex study condom, ranging from 3.50% to 4.17%. The percentage and SE of latex condoms with complete slippage was 1.11% (0.328). Percentages for Tactylon condoms were equivalent to those for latex, ranging from 0.70% to 1.31%. The Low-Modulus Tactylon condom was the most preferred. Fewer medical events were reported with the Tactylon condoms than with the latex condom. It was concluded that Tactylon condoms were equivalent to the latex condom in terms of slippage but not breakage. However, safety and acceptability seemed to be better for Tactylon condoms. This may improve consistency of use and may attract new users.

Evaluation of prostate-specific antigen as a quantifiable indicator of condom failure in clinical trials

The ability of condoms to retain all elements of semen during intercourse has been assessed by postcoital visual inspection and in vitro permeability studies. Yet, these observations may not be sufficiently precise or realistic. This pilot study evaluated prostate-specific antigen (PSA) as a semen marker of inapparent failure of the condom barrier under conditions of actual use. Twelve couples collected samples from the vagina and surfaces of the condom using sterile cotton swabs. We obtained precoital and postcoital samples for 24 acts of unprotected intercourse, 54 acts of intercourse using intact condoms, and 40 acts of intercourse using condoms that had been deliberately punctured. We used electrophoresis to determine the amount of PSA present in the samples. PSA was detected in 100% (24/24) of vaginal samples collected immediately after unprotected intercourse and in none of the vaginal samples collected more than 24 h after intercourse (0/90). PSA was also present in 98% (83/85) of the samples collected from the inside of the condom that had failed during intercourse. Excluding uses where the condom failed during intercourse, PSA was detected in 2% (1/47) of the postcoital vaginal samples collected after use of intact condoms and in 41% (14/34) of the samples collected after use of condoms with known 1-mm punctures. We conclude that PSA shows great promise as a semen biomarker in clinical trials of barrier methods. We recommend that future studies further investigate the ability of this biomarker to identify condom failures and quantify the extent of semen exposure associated with various types of condom failures.

Noncomparative Contraceptive Efficacy of Cellulose Sulfate Gel

OBJECTIVE: To estimate the 6-month cumulative probability of pregnancy, short-term adverse effects, and acceptability of cellulose sulfate vaginal contraceptive gel. METHODS: Two hundred fertile heterosexual couples were enrolled in this single-center, phase II, 6-month noncomparative study conducted at the California Family Health Council in Los Angeles, California. Couples did not desire pregnancy, were at low risk for sexually transmitted diseases, and agreed to use 3.5 mL of cellulose sulfate gel intravaginally before each coital act as their primary means of contraception. Scheduled follow-up visits took place after one menstrual cycle and at study completion, which occurred after 6 months and six menstrual cycles had elapsed. In addition, participants were instructed to call the site at the onset of each menses to review their diary cards. RESULTS: The cumulative probabilities of pregnancy during 6 months and six cycles of typical use were 13.4% (95% confidence interval [CI] 7.5–19.4%) and 13.9% (95% CI 7.7–20.2%), respectively, and during 6 cycles of correct and consistent (“perfect”) use: 3.9% (95% CI 0.0–9.2%). Slightly over one fourth of the women and one man reported experiencing gel-related adverse events, two thirds of which were mild and only possibly related to the gel. Three quarters of women and men reported that they would buy cellulose sulfate gel for contraception. CONCLUSION: Cellulose sulfate vaginal gel yields pregnancy rates comparable to nonoxynol-9 and few adverse events among couples at low risk for sexually transmitted diseases. LEVEL OF EVIDENCE: II

Effect of prophylactic antibiotics on morbidity associated with IUD insertion: Results of a pilot randomized controlled trial

The efficacy of administering an antibiotic prior to IUD insertion to reduce the risk of introducing an upper genital tract infection during the procedure has not yet been established. Two double-blind randomized studies conducted in Africa comparing a 200 mg prophylactic dose of doxycycline with a placebo did not conclusively identify a reduced risk of post-insertion pelvic inflammatory disease (PID). A clinical trial of comparable design is currently under way in the US. This multi-site trial will evaluate whether use of an antibiotic prior to insertion reduces the risk of IUD removal for all medical reasons, including upper genital tract infection, within the first three months after insertion. This paper reports on the pilot phase of this study, which was designed to test the protocols and data collection instruments in advance of the full-scale clinical trial. A total of 447 prospective IUD (TCu-380A) users were randomly assigned to receive either a 200 mg dose of doxycycline or a placebo one hour before IUD insertion. 3.6% (8/219) of participants who received the antibiotic had the device removed for medical reasons (infection, bleeding, cramping, etc.) within three months post-insertion compared to 4.5% (10/223) of participants who received the placebo. This reduction in the removal rate was not statistically significant given the limited size of the pilot study (RR = 0.81; 95% CI 0.28-2.29). Only two subjects, one from each treatment group, met the diagnostic criteria for acute PID. The overall three-month retention rate was 91.8% for the antibiotic group and 89.7% for the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)