Clinical trial NCT00760006
Conditions: Cleft Palates
Keywords: cleft secondary palate primary closure of secondary cleft palate Prophylactic Antibiotics Unasyn Cleft Palate
Sponsor: Joseph Losee
Start date: 2008-05-01; Completion date: 2015-08-01
Enrollment: 224 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to determine the efficacy of administering a single dose of preoperative antibiotics to prevent complications in patients undergoing primary closure of a cleft secondary palate. Secondary objective of this study is to evaluate the effects of preoperative antibiotics administered on post operative outcome following primary closure of cleft secondary palate. The study aims to assess the efficacy of prophylactic antibiotics in cleft surgery to

* decrease the incidence of surgical sight infections
* speed the progression of postoperative healing
* improve the final quality of wound healing achieved
* decrease the rate of palatal fistula formation

Detailed description:
During the initial clinical visit, the clinical diagnosis of a cleft secondary palate or submucous cleft will be made. Other associated clinical findings such as unilateral/bilateral cleft lip, unilateral/bilateral cleft primary palate, Veau cleft palate classification, and associated syndromic diagnosis will be recorded. The severity of the cleft palate will be documented by measuring the width of the cleft and the hard-soft palate juncture. The patients will proceed through the standardized cleft treatment protocol as mandated by their specific anatomic findings. These include possible naso-alveolar molding, lip-adhesion procedures, and cleft lip repair procedures. The patients will be followed regularly in clinic and will undergo a palatoplasty procedure to repair their cleft secondary palate when clinically indicated, typically between the age of 9 and 14 months. Patients who present for treatment late will be operated on when clinically appropriate, as determined by the plastic surgeon. A Furlow palatoplasty procedure is the typical palatoplasty procedure performed by the primary investigator, but other procedures such a Von Langenbeck pushback palatoplasty may be performed as dictated by the clinical scenario.

Subjects will be randomized via aid from statisticians in the Clinical and Translational Science Institute (CTSI) here at the University of Pittsburgh. This will enable the research pharmacist at Children's Hospital of Pittsburgh, to send either the antibiotic or the saline placebo to the operating room in a blinded manner. All subjects enrolled in the study will receive a single dose of antibiotic or saline solution (placebo control) intravenously, as the IV will already be in place as standard of card for surgery. Subjects will receive the antibiotic or the saline placebo 30 minutes prior to the initial incision in their palatoplasty procedure. The FDA approved antibiotic used for this study is Unasyn. Unasyn is a first-line measure, used by ENT surgeons at Children's Hospital of Pittsburgh for antibiotic treatment of virtually all ear, nose and throat infections. The use of Unasyn for this study is off-label as with the majority of antibiotics used with children. Subjects will receive a one time dose of 50mg/kg prior to surgery, not to exceed a total of 2gm. This constitutes the focus of the study, and is the only variation from standard treatment.

Patients will be admitted to the hospital, and will be discharged home when they are in no respiratory distress, have adequate pain control, and are able to tolerate adequate PO intake. This is generally on post-operative day 2. All patients will be prescribed pain medications. Parents will be provided with, and counseled how to properly use arm splints for 14 days postoperatively. They will also be taught how to feed the child with syringe feeds. These measures prevent the child from traumatizing the suture lines with bottles, hands and foreign bodies.

Screening procedures will consist of a medical history and physical examination by a Pediatric Plastic Surgeon to determine what type of cleft palate repair is necessary. This is the same standard exam and medical/surgical work-up that any patient would receive if they were treated by the Cleft-Craniofacial Clinic in Children's Hospital of Pittsburgh of UPMC and not enrolled in this study. This aspect of care will not vary from routine treatment. All patients will be seen in weekly postoperative follow-up in the Cleft-Craniofacial Center. Documentation of these postoperative visits will include notation of signs of surgical sight infections, such as continued fevers, erythema, swelling, discharge, dehiscence, pain, and the presence of nonviable tissue. The progression of wound healing will be quantified on a scale of 1 to 4. Wounds will be classified as Stage 1 healing when there is complete union of the mucosa, and no irregularities or separation. Stage 2 healing will be documented for wounds with minor incisional irregularities or incomplete healing. Stage 3 healing will be documented when the wound exhibits worrisome mucosal viability, partial dehiscence of the oral mucosal closure, erythema, purulent drainage, or exposure of the alloderm patch. Stage 4 healing will include patients with a palatal fistula. Any patients with clinical signs and symptoms of thrush, a fungal infection of the mouth and esophagus, will have cultures of the lesions sent to confirm the diagnosis. These patients will be immediately started on a seven day course of oral fluconazole, with an initial dose of 6mg/kg, followed by daily dose of 3mg/kg, as recommended by Dr. Andrew Nowalk, MD. Patients will be seen in clinic weekly until they have reached stage 1 healing, or until the presence of a palatal fistula is documented. We anticipate a minimum of less than 2 months to a maximum of 1 year for follow-up will be necessary to document either stage 1 healing or the presence of a palatal fistula in nearly all cases. The primary endpoints measured will be 1) the incidence of surgical sight infections, 2) the incidence of palatal fistula 3) the average time needed to achieve stage 1 healing, 4) the incidence of cases with healing delayed more than one standard deviation from the average, 5) the incidence of thrush, a fungal infection of the mouth and esophagus, and 6) the incidence of allergic/drug reactions to the study drug. Surveillance for other factors such as hospital length of stay, postoperative bleeding events, postoperative respiratory distress, and diagnosis of a sepsis will be recorded as secondary endpoints.

Data collection will include patient characteristics such as, but not limited to, Veau cleft classification, width of the cleft defect, presence of associated cleft lip or primary palate, presence of syndromic diagnosis, and use of alloderm for repair augmentation, and the administration of intraoperative steroids. The two study groups will be compared on the basis of these characteristics to determine if statistically significant differences exist between the two groups. Endpoint data will be collected as discussed above, and the outcomes for the placebo and antibiotic group will be compared.

Arms: arm 1: Unasyn® is a parenteral antibiotic that combines ampicillin with sulbactam, a beta-lactamase inhibitor. All subjects enrolled in the study will receive a single dose of antibiotic or saline solution (placebo control) intravenously, as the IV will already be in place as standard of care for surgery. The study aims to assess the efficacy of the prophylactic antibiotic in cleft surgery to: decrease the incidence of surgical site infections, speed the progression of postoperative healing, improve the final quality of wound healing achieved, and decrease the rate of palatal fistula formation. arm 2: Saline Placebo. All subjects enrolled in the study will receive a single dose of antibiotic or saline solution (placebo control) intravenously, as the IV will already be in place as standard of care for surgery. This will act as the placebo control.
Interventions: intervention 1: Unasyn intervention 2: saline solution
Intervention descriptions: intervention 1: Subjects will receive the antibiotic or the saline placebo 30 minutes prior to the initial incision in their palatoplasty procedure. The FDA approved antibiotic used for this study is Unasyn. Unasyn is a first-line measure, used by ENT surgeons at Children's Hospital of Pittsburgh for antibiotic treatment of virtually all ear, nose and throat infections. The use of Unasyn for this study is off-label as with the majority of antibiotics used with children. Subjects will receive a one time dose of 50mg/kg prior to surgery, not to exceed a total of 2gm intervention 2: Subjects will receive a one time dose of 50mg/kg prior to surgery, not to exceed a total of 2gm.

Protocol documents: