Sex: F
Vaccine: FLUA4
Symptoms: Arthralgia, Condition aggravated, Knee arthroplasty, Postoperative wound infection, Procedural pain
Clinical narrative: Uncontrolled post surgical left knee pain; Left knee wound dehiscence; This clinical trial case, initially received on 16-May-2024, was reported by a health professional and concerns an adult female subject. Weight: 118.5 kg; Height: 163 cm  The subject was enrolled in the study  Past procedures included: Left knee meniscus tear repair, Hysterectomy with oophorectomy (fibroids), Tonsillectomy, left knee repair two times in 1986, Bartholin gland cyst excision, Umbilical hernia repair.  At the time of the event the subject had Hypertension, Hyperlipidemia, Depression, Smoking cessation, Diabetes Mellitus Type 2, Gastroesophageal reflux disease, Chronic constipation, Osteoarthritis (knees), Left shoulder pain (unknown etiology), Allergy to Lortab (itching), Obstructive sleep apnea, Intramural leiomyoma of uterus, and Obesity. The subject's historical condition included Left medial meniscus tear and Hx MRSA.  Concomitant medications: atorvastatin for hyperlipidemia, hydrochlorothiazide and lisinopril for hypertension, LInzess (linaclotide) for chronic constipation, pantoprazole for gastroesophageal reflux disease, metformin and Jardiance (empagliflozin) for diabetes mellitus type 2, Wellbutrin xl (bupropion hydrochloride) for smoking cessation, vitamin d and  Lactaid extra strength (tilactase) (reported as Lactaid Oral Product') as dietary supplements, acetaminophen for osteoarthritis (knees), Aspirin low (acetylsalicylic acid) (reported as Aspirin low strength') for prophylaxis, and naproxen for left shoulder pain (unknown etiology).  The subject's historical vaccine included influenza vaccine (brand not specified) received on an unknown date in Dec-2021, on 03-Dec-2020, and on 02-Nov-2022, all three times for prophylaxis.  Administration of company suspect drug: On 29-Nov-2023 09:56, the subject received aQIVc HD  vs QIVr vs aQIV for Prophylaxis of influenza, Dose regimen: 0.5 ml, Route of administration: Intramuscular, Anatomical Location: Right Deltoid. The study vaccine was administered as per the protocol.   No additional suspect drugs.  Adverse reactions/events and outcomes: On 01-Jan-2024, the subject experienced left knee pain.  On 05-Mar-2024, three months and six days after receiving aQIVc HD vs QIVr vs aQIV, the subject experienced Uncontrolled post surgical left knee pain (Hospitalized, Disability, outcome: Recovered / Resolved, stop date: 08-Mar-2024). The subject started treatment with aceaminophen 975 mg, three times a day, cefazosin intraveonusly 2 grams, four times a day, Celebrex (celecoxib) orally 400 mg, single, Dilaudid (hydromorphone hydrochloride) intravenously 0.5 mg, as needed, docusate sodium and senna (docusate sodium, sennoside a+b) orally 50-8.6 mg, two times a day, enoxaparin subcutaneously 40 mg, every day, fentanyl intravenonusly 25 micrograms, as needed, Lactated ringers (calcium chloride, potassium chloride, sodium lactate) intravenously, single, meloxicam orally 7.5 mg, every day, oxycodone orally 10 mg, as needed, pregabalin orally 75 mg, single, RECK (ropivacaine, epinephrine, clonidine, ketorolac) 50 ml, single, and sodium chloride 0.9% intravenously 1000 ml, single.  On the same date, the subject recovered from the event of left knee pain.  On 06-Mar-2024, the subject started treatment with gabapentin 300 mg, orally, twice a day, for worsening of left knee pain.  On 08-Mar-2024, the subject recovered from the event of worsening left knee pain and uncontrolled post surgical left knee pain and was discharged from the hospital. The subject started treatment with acetaminophen 325 mg orally, three times a day, docusate sodium and senna orally 50-8.6 mg, as needed, and famotidine orally 20 mg, two times a day.  On 08-Apr-2024, the subject stopped treatment with famotidine, acetaminophen, and docusate sodium and senna.  On 29-Apr-2024, the subject stopped treatment with gabapentin.  On 30-Apr-2024, five months and 17 days after receiving aQIVc HD vs QIVr vs aQIV, the subject experienced Left knee wound dehiscence (Hospitalized, Disability, outcome: Recovering / Resolving, stop date: 01-May-2024).  On 01-May-2024, the subject was discharged from the hospital with staples that upon removal became a complex wound requiring multiple con-meds and three times a week wound care.  The subject was hospitalized for need of left TKA (total knee arthroplasty), was kept for 2 more days unknown reason.   Subject was discharged post Left knee replacement with staples that became infected, upon removal became a complex wound requiring multiple con-meds and 3 times a week wound care.   Non-drug treatment/Other action taken:  aQIVc HD  vs QIVr vs aQIV action taken: Not Applicable Treatment medication: Acetaminophen 975 mg Three times a day, 975 mg As needed, 975 mg Three times a day, Bupivacaine 20 ml Single, Buspar 5 mg Twice a day, Cefazolin 2 g Four times a day, 2 g Once a day, Celebrex 400 mg Single, Celecoxib 200 mg Single, Dexamethasone 8 mg Single, Dilaudid .5 mg As needed, Docusate sodium and senna 1 DF , 1 DF As needed, Doxycycline monohydrate 100 mg Twice a day, Enoxaparin 40 mg Every day/daily, Fentanyl 25 µg As needed, Gabapentin 300 mg Twice a day, 300 mg Twice a day, 600 mg Single, Insulin lispro 5 iU Three times a day, Lactated ringers   , Meloxicam 7.5 mg Every day/daily, Methocarbamol 500 mg Three times a day, Oxycodone 10 mg As needed, 10 mg As needed, 5 mg Four times a day, Pregabalin 75 mg Single, Robaxin 500 mg Three times a day, Ropivacaine 50 ml Single, Sodium chloride 1000 ml Single  Reporter's assessment: The Investigator assessed the events as severe and serious due to seriousness criterion of hospitalization. The events were assessed as not related to the study vaccine and the alternative cause for the events was reported as concomitant disease.  The subject remained blinded in the study.   Follow-up (21-May-2024) received from the Investigator: The subject's height and weight were added. Hypertension, recurrent otitis media, hyperlipidemia, depression, smoking cessation, diabetes mellitus type 2, gastroesophageal reflux disease, chronic constipation, osteoarthritis (knees), left shoulder pain (unknown etiology), obesity, left knee meniscus tear repair, hysterectomy with oophorectomy (fibroids), and tonsillectomy were added in Other Relevant History section. Atorvastatin, hydrochlorothiazide, lisinopril, pantoprazole, metformin, Jardiance, Wellbutrin xl, vitamin d, Lactaid extra strength, Aspirin low, and naproxen were added as concomitant medications. The narrative was updated accordingly.  Follow-up (30-May-2024) received from the Investigator: Acetaminophen, bupivacaine, cefazolin, celecoxib, dexamethasone and gabapentin added as treatment medication. The narrative was updated accordingly.  Follow-up (07-Jun-2024) received from the Investigator: cefazolin and dexamethasone deleted from treatment medication.  The narrative was updated accordingly.  Follow-up (12-Jun-2024) received from the Investigator: cefazolin and dexamethasone added as treatment medication. Left knee repair added as procedure. Left medial meniscus tear added as historical condition.  The narrative was updated accordingly.  Follow-up (26-Jun-2024) from the Investigator: Depression added as additional indication for concomitant medication Wellbutrin xl. Buspar (buspirone hydrochloride), oxycodone and doxycycline monohydrate were added as treatment medication. No changes in the narrative.  Follow up (02-Jul-2024) received from Investigator: Concurrent condition recurrent otitis media deleted. Indication for treatment medication cefazolin changed form prophylaxis left knee wound dehiscence to left knee wound dehiscence, and stop date changed from 01-May-2024 to 30-Apr-2024. Narrative amended accordingly.  Follow up (24-Jul-2024) received from Investigator: The event of 'postoperative pain' added. The subject's medical history updated with allergy to Lortab, obstructive sleep apnea on CPAP, umbilical hernia repair, intramural leliomyoma of uterus, left knee repair, and Hx MRSA. Treatment medications famotidine, sodium chloride, pregabalin, meloxicam, Celebrex, Dilaudid, docusate sodium and senna, enoxaparin, fentanyl, Lactated rings, oxygen, and RECK (ropivacaine, epinephrine, clonidine, ketorolac) added. Additional doses and indications added for treatment medications  acetaminophen, cefazolin, gabapepntin, and oxycodone. The narrative amended accordingly.  Follow up (30-Jul-2024) received from Investigator: Current condition was changed from 'Obstructive sleep apnea on CPAP' to 'Obstructive sleep apnea'. Serious adverse event Worsening left knee pain' (LLT: Arthralgia aggravated') was deleted. Two influenza vaccines added as historical vaccines. Indication for treatment Acetaminophen changed from Worsening left knee pain' to Left knee post operative pain' and from Left knee wound dehiscence' to Worsening left knee pain'. Formulation added and dose changed for treatment Docusate sodium and senna. Treatment Ropivacaine-Epinephrine-Clonidine-Ketorolac (RECK)' was changed to Ropivacaine Product' and coded as ropivacaine. Treatments insulin lispro, Robaxin (methocarbamol) and methocarbamol were added. Dosage regimen added for treatment oxycodone. Stop date added for treatment doxycycline monohydrate. Seriousness criterion of disability was marked for the events of Wound dehiscence' and Postoperative pain'. Seriousness criteria of congenital anomaly and medical significance were negated for the event of Postoperative pain'.Narrative amended accordingly.  Follow up (17-AUG-2024) received from Investigator: New medical history "Left medial meniscus tear repair #2" added. Narrative updated accordingly.  Follow-up (29-Aug-2024 and 30-Aug-2024) received from an Investigator: Added summery description of event and updated indication of treatment medication, Updated narrative accordingly.  Follow-up (13-Nov-2024) received from  investigator: stop date provided for event (left knee wound dehiscence), no changes in outcome. Field and narrative updated accordingly.; Reporter's Comments: An adult subject was hospitalized due to uncontrolled post-surgical pain three months and six days after receiving blinded study vaccine aQIVc HD vs QIVr vs aQIV. Five months and 17 days after receiving aQIVc HD vs QIVr vs aQIV, the subject was hospitalized due to left knee wound dehiscence. Subject was dismissed from the hospital with staples that upon removal became complex wound which required multiple con-meds and frequent wound care. In line with Investigator's causality assessment, Sponsor agreed and assessed both events as not related to the blinded study vaccine, due to biological and chronological implausibility. Of note, subject had a history of two previous left knee surgeries that can provide an alternative explanation for the events. Osteoarthritis, obesity, and diabetes mellitus type 2 may have further contributed to the development of the events. Listedness was assessed using IB version 4.