Non-inferiority of short-term urethral catheterization following fistula repair surgery: study protocol for a randomized controlled trial

A vaginal fistula is a devastating condition, and while true prevalence is unknown, it is estimated to affect 2 million girls and women across Africa and Asia. The primary cause of a vaginal fistula is prolonged obstructed labor: the fetus's head compresses the soft tissues of the bladder, vagina and rectum against the woman's pelvis, cutting off blood supply to the tissue, causing the tissue to die and slough away. The result is an abnormal opening between the vagina and bladder, or between the vagina and rectum, or both, and either urinary and/or fecal incontinence.

Approximately 80-95% of vaginal fistula can be closed surgically [1]; however, the provision of fistula repair services in developing countries is not without challenges. Specialized training and skills are necessary, especially to handle more complex cases, and this limits the availability of services. Women with fistula are predominantly poor and from rural areas, and often cannot pay for surgery or transport to a service site. Thus, fistula repair services must be provided free of charge. Fistula services are few and far between in Africa and Asia: the availability of services depends not only on the availability and motivation of surgeons with specialized skills, but also the availability of operating rooms, equipment, and funding from local or international donors to support both surgeries and lengthy post-operative care. In most contexts, the need for repair services exceeds the available human and infrastructural capacity. Moreover, the prolonged bladder catheterization that is frequently employed after surgery translates into a need for longer hospitalization, more intensive nursing care, and increased costs, leading to decreased capacity for treating other patients. Longer duration catheterization may also be associated with increased risk of healthcare-associated infection. Reducing the duration of bladder catheterization, provided no compromise in surgical outcomes and patient health, has important implications for the delivery of fistula care and treatment services in low resource settings.

Bladder catheterization practices following fistula repair and other pelvic surgery vary. Publications about fistula surgery often state that bladder drainage through indwelling urethral catheterization should continue between 10 and 14 days post-operatively [2, 3]. However, in both fistula repair [4] and other types of gynecological surgery [5], the duration of bladder drainage via indwelling urinary catheter is primarily based on custom rather than empirical research, and the duration of drainage varies substantially. A recent survey of 40 fistula surgeons conducted by Arrowsmith and colleagues [6] found that catheterization durations following fistula repair surgery ranged from 5 to 21 days, with 13% of surgeons reporting they catheterize women for 8 days or less following surgical repair of simple fistula. Results from a multi-country prospective cohort study examining predictors of repair outcomes recently completed by Fistula Care/USAID also found a wide distribution in post-repair duration of urethral catheterization among 1274 women. The median duration of catheterization was 21 days, with an interquartile range (IQR) of 14-27 days [7]. A wide range has also been found for duration of catheterization following colovesical fistula repair. A retrospective review of data at Massachusetts General Hospital conducted by de Moya and colleagues found that duration of catheterization following colovesical fistula repair secondary to diverticulitis ranged from 3-42 days [8]. While colovesical fistula repairs differ considerably from vaginal fistula repairs, these findings nonetheless indicate that not only is shorter-term catheterization currently being implemented for different types of bladder surgery, but that it may be a feasible alternative to longer term catheterization following the repair of simple urinary fistula in women.

Short-term urethral catheterization may in fact pose no additional risk to patients in terms of repair prognosis. One purpose of post-repair urethral catheterization is to provide an opportunity for adequate tensile strength to develop so that bladder distension does not disrupt the healing wound. The presumption behind prolonged catheterization is that the bladder heals better "at rest" (i.e. when it is not filling and emptying); however, there is little evidence to support this. For non-contaminated wound healing in general, the critical period involving granulation and neovascularization peaks at 5 days and inflammation is over in 1 week [9], with matrix deposition and cell proliferation continue until at least 30 days. Tensile strength increases rapidly during the first 5 days, although final tensile strength is not reached until over 100 days. A recent study evaluating the effects of long-term catheterization on extracellular matrix (ECM) biological scaffold remodeling following partial cystectomy in canines, found that early bladder filling (i.e. shorter duration of catheterization) mediated a constructive remodeling response [10]. While biologic scaffolds composed of ECM are a cutting edge innovation not feasible for fistula repair in developing countries, these results suggest that removing the catheter early and allowing the bladder to begin filling and emptying, may be beneficial, rather than harmful, to bladder healing. Nonetheless, no basic physiologic studies on the dynamics of wound healing in the bladder after fistula repair have been published to date and it is possible that the wound healing process following fistula repair may be more prolonged than noted above given the contaminated and chronic nature of most vaginal fistula.

Given the potential benefits of short-term urethral catheterization, and the fact that it is currently being practiced by some fistula surgeons, empirical evidence is needed to determine the non-inferiority of short-term urethral catheterization compared to longer-term urethral catheterization. The primary objective of this study is thus to examine whether short-term (7 day) urethral catheterization is not worse by more than a minimal relevant difference to longer-term (14 day) urethral catheterization in terms of incidence of fistula repair breakdown among women with simple fistula.

This will be a non-inferiority randomized controlled trial (RCT) comparing the new proposed short-term (7 day) urethral catheterization to longer-term (14 day) urethral catheterization in terms of predicting fistula repair breakdown, measured 3 months following fistula repair surgery. This study will be conducted among 512 women with simple fistula presenting at eight study sites for fistula repair surgery (Table 1). Figure 1 depicts the flow of study participants.

If no major safety issues are identified, the data from this trial may facilitate adoption of short-term catheterization following repair of simple fistula in various countries in sub-Saharan Africa and Asia. The adoption of short-term catheterization will have important implications for service delivery, and potentially, patient health outcomes. For instance, Nardos and colleagues calculated the implications of urethral catheterization duration at the Addis Ababa Fistula Hospital, where approximately 1200 fistula repairs are performed annually. They reported that assuming no compromise in patient outcomes, a four day reduction in postoperative hospitalization due to early bladder catheter removal (10 vs. 14 days) would allow the number of patients who could receive surgical care to be increased by 20% [9]. In light of the wide range of catheterization durations practiced in sub-Saharan Africa and Asia [6, 7], the potential benefit associated with short-term catheterization with regard to increased access to surgery for women with obstetric fistula may be significantly greater. In addition, short-term duration of urethral catheterization may also decrease risk of urinary tract infection (UTI). For instance, a recent Cochrane review of urinary catheterization following urogenital surgery in adults examined seven trials which compared shorter postoperative duration of catheter use to longer duration; these trials suggested that shorter-term catheterization was associated with fewer UTIs [13]. In sum, short-term urethral catheterization has the potential to reduce hospital stays for women, thus freeing bed space, reducing costs per patient, and allowing for a greater number of patients to receive clinical care. It may also have implications for the probability of infection, and possibly sepsis, following surgery. Irrespective of study outcome, the results of this study will be disseminated in at least one workshop/forum attended by fistula surgeons, regional/local meetings, and at least one publication in a peer-reviewed journal.

The protocol received technical and ethical approval from the WHO Research Project Review Panel (RP2) and Research Ethics Review Committee, respectively. Ethical approval will be obtained from appropriate national and institutional ethical review bodies as applicable for each study site. Recruitment of participants at any given site will not begin until all the necessary local ethical approvals have been obtained.