Trimethoprim/Sulfamethoxazole Combined With Caspofungin as First-line Therapy in PCP

Study Overview
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Brief Summary
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This is a prospective, randomized clinical trial. During the study, non-HIV patients who are admitted to ICU due to Pneumocystic pneumonia (PCP) and have not received anti-PCP therapy or have received therapy less than 48hrs will be randomized (1:1) to received caspofungin combined with trimethoprim-sulfamethoxazole or trimethoprim-sulfamethoxazole alone. The aim of this study is to compare the effectiveness of caspofungin combined with trimethoprim-sulfamethoxazole with that of conventional therapy (trimethoprim-sulfamethoxazole alone) as first-line therapy in the treatment of severe Pneumocystis pneumonia (PCP) in non-HIV patients.

Official Title
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A Prospective Randomized Controlled Study to Compare Efficacy of Caspofungin Combined With Trimethoprim-sulfamethoxazole Versus Trimethoprim/Sulfamethoxazole as First-line Therapy in Non-HIV Patients With Severe Pneumocystis Pneumonia

Conditions
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Pneumocystis Pneumonia

Intervention / Treatment
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* Drug: caspofungin
* Drug: TMP/SMZ(trimethoprim/sulfisoxazole)
* Drug: Methylprednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old Non-HIV immunosuppressed patients admitted to the ICU confirmed or suspect PCP 3) Not receiving anti-PCP treatment or anti-PCP treatment < 48 hours Exclusion Criteria: Age less than 18 years old Known pregnancy allergy to TMP/SMZ or caspofungin Decision to withhold life-sustaining treatment Patients with advanced pulmonary fibrosis severe liver dysfunction(Child-Pugh C )

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAS with TMP/SMZ<br> | Drug: caspofungin<br>* caspofungin 70mg ivdrip the first day, then 50mg ivdrip qd for 21days<br>Drug: TMP/SMZ(trimethoprim/sulfisoxazole)<br>* TMP:15mg/kg/d for 21 days +SMZ:75mg/kg/d for 21days<br>Drug: Methylprednisolone<br>* 40mg ivdrip q12h for 5 days , then 40mg ivdrip qd for 5 days , 20mg for 11 days<br>|
| Active Comparator: TMP/SMZ<br> | Drug: TMP/SMZ(trimethoprim/sulfisoxazole)<br>* TMP:15mg/kg/d for 21 days +SMZ:75mg/kg/d for 21days<br>Drug: Methylprednisolone<br>* 40mg ivdrip q12h for 5 days , then 40mg ivdrip qd for 5 days , 20mg for 11 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality to day 28 | The percentage of subjects death at study day 28. Those subjects discharged from ICU prior to day 28 were counted as alive at day 28 | 28 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU Free Days to day 28 | defined as the number of days between randomization and day 28 in which the patient is not in the ICU (for any part of a day) | 28 days after randomization | 
| Mean Ventilator Free Days to day 28 | Ventilator-free days is defined to be 28 days minus the duration of mechanical ventilation through day 28. Participants who do not survive to day 28 are assigned zero ventilator-free days. | 28 days after randomization | 
| ICU mortality | The percentage of death subjects at ICU discharge | through ICU discharge, an average of 14 days | 
| hospital mortality | The percentage of death subjects at hospital discharge | through hospital discharge, an average of 28 days | 
| PO2/FiO2 on day 7, 21 | the change of PO2/FiO2 between baseline and day7, 21 | day 7, 21 after randomization | 
| serum (1,3)-β-D gluca level on day 3, 7, 21 | the change of (1,3)-β-D glucan level between baseline and day3, 7, 21 | day3, 7, 21 after randomization | 
| PCP-DNA negative conversion rate in alveolar lavage fluid on day 7 after randomization | the percentage of PCP-DNA negative after 7days treatment | day 7 after randomization | 
| SOFA | respiratory dysfunction assessed by Sequential Organ Failure Assessment (SOFA) score for respiratory system | day3, 7, 21 after randomization | 
| BALF cytokines level on day3, 7, 21 | the change of cytokines in bronchoalveolar lavage fluid (BALF) level between baseline and day7, day21 | day3, 7, 21 after randomization | 
| adverse events | incidence, duration and severity of adverse events | till 21 days after randomization | 
| serious adverse events | incidence, duration and severity of serious adverse events | till 21 days after randomization |