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

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

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.

Study Overview

• Status: Unknown
• Conditions: Pneumocystis Pneumonia
• Intervention / Treatment: Drug: caspofungin; Drug: TMP/SMZ(trimethoprim/sulfisoxazole); Drug: Methylprednisolone

• Study Type: Interventional
• Enrollment (Anticipated): 122
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Bin Du; Phone Number: 0086-10-69155036; Email: dubin98@gmail.com
• Study Contact Backup: Name: JINMIN PENG; Phone Number: 0086-10-69154040; Email: pjm731@hotmail.com

Study Locations

• China
  • Beijing, China, 100730
    • Recruiting
    • MICU of Peking Union Medical College
    • Contact: Bin Du, Dr; Phone Number: (8610)69155036; Email: dubin98@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years old
2. Non-HIV immunosuppressed patients admitted to the ICU
3. confirmed or suspect PCP

3) Not receiving anti-PCP treatment or anti-PCP treatment < 48 hours

Exclusion Criteria:

1. Age less than 18 years old
2. Known pregnancy
3. allergy to TMP/SMZ or caspofungin
4. Decision to withhold life-sustaining treatment
5. Patients with advanced pulmonary fibrosis
6. severe liver dysfunction(Child-Pugh C )

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bin Du

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2019
• Primary Completion (Anticipated): June 20, 2022
• Study Completion (Anticipated): July 8, 2022

Study Registration Dates

• First Submitted: June 5, 2019
• First Submitted That Met QC Criteria: June 5, 2019
• First Posted (Actual): June 7, 2019

Study Record Updates

• Last Update Posted (Actual): September 12, 2019
• Last Update Submitted That Met QC Criteria: September 11, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections and Mycoses; Mycoses; Lung Diseases, Fungal; Pneumocystis Infections; Pneumonia; Pneumonia, Pneumocystis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuroprotective Agents; Protective Agents; Cytochrome P-450 Enzyme Inhibitors; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Folic Acid Antagonists; Anti-Dyskinesia Agents; Anti-Infective Agents, Urinary; Renal Agents; Cytochrome P-450 CYP2C8 Inhibitors; Methylprednisolone; Caspofungin; Trimethoprim; Sulfisoxazole
• Other Study ID Numbers: MICU-PCP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No