Health Condition 1: K74- Fibrosis and cirrhosis of liver
Conditions
Interventions
Intervention1: Early empiric group: Participants will receive standard medical therapy
along with the empiric strategy of treatment of invasive
fungal infection (based on both risk factors and
clinica
Sponsors
ICMR
Eligibility
Inclusion criteria
Inclusion criteria: ACLF patients aged 18 to 75 years with all three following criteria will be included: 1. ICU stay of 48 hours or recent hospitalization 2. Two or more risk factors for IFI of the from the below mentioned: a. Mechanically ventilated at least = 48 hours b. Treatment with broad-spectrum antibacterial agents for more than 3 days c. Arterial or central vein catheter = 2days d. Diabetes Mellitus e. Total parenteral nutrition = 48 hours f. Acute renal failure requiring any form of renal replacement therapy =48hours g. Pancreatitis related hospitalization > 7days in last 3 months h. Steroid use, immunosuppressant use in the preceding 30 days i. High disease score as defined as MELD=20 or APACHE II =16 j. Refractory ascites, norfloxacin prophylaxis k. Gastrointestinal tract surgery, abdominal perforation or anastomotic leaks or any invasive procedures or surgeries in the last 7days l. Chronic pulmonary diseases including COPD or Tuberculosis m. Moderate to severe sarcopenia as defined by The Royal Free Hospital-global assessment (RFH-GA) scale60 (As per Appendix “4 ? ) n. Firm diagnosis of H1N1 influenza infection in the last 3 months 3. Clinical suspicion of IFI as defined by any of the following: a. Evidence of unresolved sepsis/SIRS(= 2/4) despite appropriate broad-spectrum antibiotics beyond 3days b. Recrudescence of fever after a period of defervescence of at least 48 hours while still on antibiotics and without other apparent cause c. Tracheobronchial ulcer, nodule, plaque or pseudo-membrane d. Sino-nasal infection: features of acute sinusitis with at least 1 of acute localized pain, nasal ulcer, eschar, orbital involvement or e. Respiratory symptoms: • Worsening respiratory insufficiency despite appropriate ventilator support and antibiotics • Any 2 of Pleuritic chest pain, pleural rub, dyspnea, hemoptysis f. Characteristic skin lesions suspected of fungal infection g. Unexplained worsening of encephalopathy after initial improvement
Exclusion criteria
Exclusion criteria: 1. Neutrophil count of less than 500/mm3 2. Current or recent antifungal treatment in the past 1 months 3. Hepatocellular carcinoma or other active malignancy 4. Known hypersensitivity or contraindication to Liposomal AmB or any other AmB preparation 5. Human immunodeficiency virus seropositivity on rapid card test/ELISA, or currently on combination antiretroviral therapy (cART) 6. Pregnancy as confirmed by urine pregnancy test or lactation 7. Moribund patients as defined as a. = 4 organ failure as per CLIF-SOFA score b. Signs of brainstem death- absent brainstem reflexes c. Expected ICU stay
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survivalTimepoint: 28 day | — |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of proven or probable IFI at 28 daysTimepoint: 28 days;In-hospital mortality- Number of participants dying in hospital due to any cause within 28 day of enrollment Timepoint: 28 days;Evolution of organ failures as assessed by chronic liver failure-sequential organ failure score (CLIF-SOFA)-Development of new or worsening organ failures as defined by chronic liver failure -sequential organ failure (CLIFSOFA) scores within 28 days of enrollment. CLIF-SOFA score ranges from 0-24 incorporating 6 organ systems and 0 being best and 24 being worstTimepoint: 28 days;Evolution of serum 1, 3 Beta-D Glucan (BDG; in pg/ml) levels throughout the study period- Trends of 1, 3 Beta-D Glucan (BDG) throughout the study period that will be done on twice weekly intervals after enrollmentTimepoint: 28 days;Evolution of serum Galactomannan index (GM; in %) throughout the study period- Trends of Galactomannan index (GM; in %) throughout the study period that will be done on twice weekly intervals after enrollmentTimepoint: 28 days;Incidence of key events like new onset ventilator associated pneumonia, urinary tract infection, spontaneous fungal peritonitis- Incidence of key events like new onset VAP, UTI, fungal SBPTimepoint: 28 days;Mechanical ventilation free days- Duration free from mechanical ventilation within 28 days of enrollmentTimepoint: 28 days;Length of ICU and hospital stay- Effect on length of ICU, hospital stay within 28 day of enrollmentTimepoint: 28 days;Treatment success rate- Treatment success rate, successful treatment being defined as a. Survival beyond 7 days of start of SAT with resolution of sepsis attributable to IFI b. Absence of new/ breakthrough IFI during treatment or within 7 days of completion c. Absence of treatment discontinuation related to toxicity/lack of efficacyTimepoint: 28 days;Number of participants with adverse events due to antifungals requiring cessation of therapy- Number of participants out of whole group who would develop adv | — |
Countries
India
Contacts
Public ContactDr Nipun Verma
PGIMER, Chandigarh
Outcome results
None listed