PROMComplete for Determination of Rupture of Fetal Membranes

Study Overview
=================
Brief Summary
-----------------
Premature rupture of membranes refers to the rupture of the fetal membranes prior to the onset of labor. Premature rupture of membranes is associated with a number of neonatal and maternal complications including an increased incidence of perinatal mortality and intra-amniotic infection. There is a need for improved diagnostic testing because of limitations of the current methods. PRO-MComplete is an immunochromatographic test that detects insulin growth factor binding protein 1 and alpha-fetoprotein in vaginal fluid as an indicator of membrane rupture.

Detailed Description
-----------------
Premature rupture of membranes (PROM) complicates approximately 8 % of pregnancies and is generally followed by the prompt onset of spontaneous labor and delivery. Preterm PROM complicates only 2 % of pregnancies but is associated with 40% of preterm deliveries and can result in significant neonatal morbidity and mortality (ACOG 2007). Intraamniotic infection has been shown to be commonly associated with preterm PROM, especially at earlier gestational ages (ACOG 2013). Currently, the diagnosis of PROM is based primarily on the patient's history and physical examination. The diagnosis of membrane rupture typically is confirmed by the visualization of amniotic fluid passing from the cervical canal and pooling in the vagina; a basic pH test of vaginal fluid; or arborization (ferning) of dried vaginal fluid, which is identified under microscopic evaluation (ACOG 2013). The classic clinical presentation of PROM is a sudden gush of clear or pale yellow fluid from the vagina. However, many women describe intermittent or constant leaking of small amounts of fluid or just a sensation of wetness within the vagina or on the perineum (WHEC 2009). However, the diagnosis of PROM is difficult if there is a slow fluid leak or any bleeding, or when the classic gush of fluid does not occur (Bornstein 2006). Although ultrasonographically guided transabdominal instillation of indigo carmine dye and observation for fluid passage transvaginally is designated an unequivocal diagnostic method for confirmation of membrane rupture, this invasive test carries increased maternal and fetal risk (Mercer 2004). The absence of a non-invasive gold standard for the diagnosis of PROM has led to technically advanced biochemical markers for improved diagnosis (El-Messidi, 2010). The AmniSure ROM (Rupture of Membranes) test received Food and Drug Administration 510(k) marketing clearance in 2003. A comparison study of AmniSure versus standard diagnostic methods for detection of ROM in 203 pregnant women suspected of ROM reported that the AmniSure test was highly accurate (sensitivity = 98.9 %, specificity = 100 %, and negative predictive value [NPV] = 99.1 %) in diagnosing ROM (Cousins et al, 2005). Test performance was calculated by comparing AmniSure results against clinical history, nitrazine and fern results, presence of pooling, ultrasound (US) evidence of oligohydramnios, and findings from repeated examinations. Chen and Dudenhausen (2008) compared 2 rapid strip tests for the detection of amniotic fluid, based on the detection of insulin-like growth factor-binding protein-1 (IGFBP-1) and of PAMG-1. Samples of amniotic fluid were taken in 20 pregnant women between 31 3/7 and 41 2/7 gestational weeks at elective cesarean section before delivery of the newborn. These samples were diluted with 0.9 % saline solution in a dilution series down to concentrations of 1:320. Immunoassay strip tests were then compared in their ability to detect remaining concentrations of amniotic fluid. In 5 cases, both test methods showed the same results. In all remaining 15 cases, the test based on PAMG-1 proved to be superior by detecting amniotic fluid at least at one descending concentration below the test based on IGFBP-1. PRO-MComplete proposes an alternative tool for adjuvant diagnosis of PROM by identification of Insulin-Like Growth Factor Binding Protein1 and Alpha Feto- Protein (AFP). The addition of AFP is projected to increase the sensitivity and specificity of PRO-MComplete over IGFBP-1 alone.

Official Title
-----------------
Clinical Evaluation of PRO-MComplete as an Aid in Determination of Rupture of Fetal Membranes

Conditions
-----------------
Fetal Membranes, Premature Rupture

Intervention / Treatment
-----------------
* Other: non- intervention study


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject has provided verbal and written informed consent to participate in the study. 20-42 weeks of gestation. Subject presents with signs and/or symptoms of premature rupture of membranes. Subject age 18 (years) or older Exclusion Criteria: Placenta Previa Presenting with vaginal bleeding Intravaginal ultrasound with presence of transducer gel Active labor Imminent delivery Intercourse within 24 hours Cord prolapse

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: non- intervention study|Study design is non-interventional. Patient therapy will not be affected by study participation.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| accuracy of Pro-mcomplete vs conventional testing for ruptured fetal membranes | All eligible subjects will be evaluated clinically and will be tested with appropriate reference tests as well as the PRO-MComplete test. Subjects tested with Pro-mcomplete will be followed until delivery of index pregnancy. Final subject evaluation will occur with index delivery. | up to 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of discordant examination | Documentation of frequency of device and clinical examination incongruent results. Pregnancy outcomes will be reviewed for all test subjects, not just the test incongruent cohort. | up to 20 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alfa-fetoprotein, amniorrhexis, Ruptured membranes