Pilot Feasibility Study With Patients Who Are at High Risk For Developing Invasive Candidiasis in a Critical Care Setting (MK-0991-067)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01045798
• Collaborator: Mycoses Study Group (Other)
• Enrollment: 15
• Arms: 2
• Duration (Months): 16

Study Details

Study Description

Brief Summary

This is a pilot feasibility study that investigates antifungal therapy with caspofungin in patients at high-risk for developing invasive candidiasis in a critical care setting.

Condition or Disease	Intervention/Treatment	Phase
Invasive Candidiasis	Drug: Caspofungin acetate; Drug: Placebo	Phase 2

Detailed Description

Hypothesis: In high-risk non-neutropenic participants in the ICU, the proportion of participants discontinued from study therapy in order to be empirically treated with antifungal therapy for suspected candidiasis outside of the context of this protocol is less than 20% (i.e., the upper bound of the 95% confidence interval for the observed proportion is less than 20%).

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: MSG-04 (Also Known as Merck Caspofungin Protocol 067): A Pilot, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Caspofungin Empirical Therapy for Invasive Candidiasis in High-Risk Patients in the Critical Care Setting
• Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Caspofungin caspofungin acetate	Drug: Caspofungin acetate; 70 mg of caspofungin administered intravenously (IV) on Day 1 followed by 50 mg daily for at least 6 additional days (maximum duration study therapy is 14 days); Other Names: caspofungin MK-0991 Cancidas®
Placebo Comparator: Placebo normal saline	Drug: Placebo; Placebo to caspofungin (normal saline) on Day 1 followed by placebo daily for at least 6 additional days (maximum duration study therapy is 14 days); Other Names: normal saline

Outcome Measures

Primary Outcome Measures

1. The Proportion of Patients Discontinued From Study Therapy to be Treated With Empirical Antifungal Therapy Outside of the Context of the Study. [1 to 14 days]

   The feasibility of conducting a major randomized study of caspofungin for empirical therapy for invasive candidiasis in high-risk non-neutropenic intensive care unit (ICU) participants was to be assessed by the incidence of study therapy discontinuations due to investigators choosing to treat participants with empirical antifungal therapy outside of the context of this protocol. Study drug was administered for a minimum of 7 days to a maximum of 14 days provided participants had no evidence of confirmed breakthrough invasive Candida infection while receiving study drug.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Hospitalization for a minimum of 3 days in an ICU and expectation to stay in the ICU for at least another 48 hours

• Meets the following high-risk criteria: Requires mechanical ventilation at the time of study entry; and has a central venous catheter in place at the time of study entry; and is receiving broad spectrum antibiotics at the time of study entry; AND meets at least one of the following criteria: Required parenteral nutrition during the current ICU admission; or required renal dialysis during the current ICU admission; or had major surgery during or within the 7 days before the current ICU admission; or was diagnosed with pancreatitis during or within the 7 days before the current ICU admission; or required systemic steroids or other immunosuppressive agents during or within the 7 days before the current ICU admission

• Meets at least one of the following criteria of suspected infection at the time of study entry or within the 24 hours before study entry: Temperature ≥38° C or ≤36° C (oral equivalent); or hypotension (systolic blood pressure of <90 mm Hg) or significant drop in blood pressure (40 mm Hg) from the participant's normal baseline; or elevated white blood cell count of ≥12,000/mm^3

• Candida is growing in at least one non-sterile culture site collected during the current ICU admission

• Female of childbearing potential has a negative serum or urine pregnancy test before enrollment

Exclusion Criteria:

• Females pregnant or breast feeding

• History of allergy, hypersensitivity, or any serious reaction to caspofungin or another member of the echinocandin class (e.g., micafungin, anidulafungin)

• Neutropenia or expected to develop neutropenia during study therapy

• Diagnosis of acquired immune deficiency syndrome (AIDS), aplastic anemia, or chronic granulomatous disease

• Diagnosis of moderate or severe hepatic insufficiency

• Patient not expected to survive at least 24 hours

• Received systemic (IV or oral) antifungal therapy within 10 days before study entry

• Active diagnosis of proven or probable invasive fungal infection (IFI)

• Currently on or has received an investigational agent within 10 days before study entry

• Any condition or concomitant illness which might confuse the study results or pose additional risk in administering the study therapy

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC
• Mycoses Study Group

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT01045798
• Other Study ID Numbers: 0991-067; 2010_502
• First Posted: Jan 11, 2010
• Last Update Posted: Mar 24, 2017
• Last Verified: Feb 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Merck Sharp & Dohme LLC: Candidiasis; Invasive Candidiasis; Fungal Infection; Empirical Therapy
• Additional relevant MeSH terms: Candidiasis; Candidiasis, Invasive; Caspofungin

Study Results

Participant Flow

Pre-assignment Detail	This study was terminated early due to low participant enrollment. One of the 15 participants randomized to treatment inappropriately received a systemic antifungal agent before starting study drug and was not included in the baseline characteristics, safety, or efficacy analyses.

Arm/Group Title	Caspofungin	Placebo
Arm/Group Description	Caspofungin 70 mg caspofungin administered intravenously (IV) on Day 1 followed by 50 mg daily for at least 6 additional days (maximum duration study therapy is 14 days)	Placebo to caspofungin (normal saline) on Day 1 followed by placebo daily for at least 6 additional days (maximum duration study therapy is 14 days)
Period Title: Overall Study
STARTED	6	9
COMPLETED	4	5
NOT COMPLETED	2	4

Baseline Characteristics

Arm/Group Title	Caspofungin	Placebo	Total
Arm/Group Description	Caspofungin 70 mg caspofungin administered intravenously (IV) on Day 1 followed by 50 mg daily for at least 6 additional days (maximum duration study therapy is 14 days)	Placebo to caspofungin (normal saline) on Day 1 followed by placebo daily for at least 6 additional days (maximum duration study therapy is 14 days)	Total of all reporting groups
Overall Participants	6	8	14
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.2 (20.1)	53.0 (10.6)	56.1 (15.1)
Sex: Female, Male (Count of Participants)
Female	3 50%	4 50%	7 50%
Male	3 50%	4 50%	7 50%

Outcome Measures

1. Primary Outcome

Title	The Proportion of Patients Discontinued From Study Therapy to be Treated With Empirical Antifungal Therapy Outside of the Context of the Study.
Description	The feasibility of conducting a major randomized study of caspofungin for empirical therapy for invasive candidiasis in high-risk non-neutropenic intensive care unit (ICU) participants was to be assessed by the incidence of study therapy discontinuations due to investigators choosing to treat participants with empirical antifungal therapy outside of the context of this protocol. Study drug was administered for a minimum of 7 days to a maximum of 14 days provided participants had no evidence of confirmed breakthrough invasive Candida infection while receiving study drug.
Time Frame	1 to 14 days

Outcome Measure Data

Analysis Population Description

Of the 114 participants anticipated to enroll in this study, 15 actually enrolled and only 14 received study drug. The participant who did not receive study drug was discontinued; the remaining 14 received at least one dose of study drug, met inclusion/exclusion criteria, and therefore qualified for the full analysis set used for summary analyses.

Arm/Group Title	Caspofungin	Placebo
Arm/Group Description	Caspofungin 70 mg caspofungin administered intravenously (IV) on Day 1 followed by 50 mg daily for at least 6 additional days (maximum duration study therapy is 14 days)	Placebo to caspofungin (normal saline) on Day 1 followed by placebo daily for at least 6 additional days (maximum duration study therapy is 14 days)
Measure Participants	6	8
Number [Participants]	1 16.7%	2 25%

Adverse Events

Time Frame	First dose of study drug through up to 14 days post-treatment
Adverse Event Reporting Description	All participants who received at least one dose of study drug were included in the safety analyses.
Arm/Group Title	Caspofungin		Placebo
Arm/Group Description	Caspofungin 70 mg caspofungin administered intravenously (IV) on Day 1 followed by 50 mg daily for at least 6 additional days (maximum duration study therapy is 14 days)		Placebo to caspofungin (normal saline) on Day 1 followed by placebo daily for at least 6 additional days (maximum duration study therapy is 14 days)
All Cause Mortality
	Caspofungin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Caspofungin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/6 (50%)		3/8 (37.5%)
Cardiac disorders
Cardiac arrest	1/6 (16.7%)		0/8 (0%)
Renal and urinary disorders
Calculus urethral	0/6 (0%)		1/8 (12.5%)
Renal abscess	0/6 (0%)		1/8 (12.5%)
Respiratory, thoracic and mediastinal disorders
Pneumonia due to Pseudomonas	0/6 (0%)		1/8 (12.5%)
Respiratory failure	2/6 (33.3%)		1/8 (12.5%)
Surgical and medical procedures
Tracheostomy	1/6 (16.7%)		0/8 (0%)
Vascular disorders
Hypotension	1/6 (16.7%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Caspofungin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/6 (66.7%)		6/8 (75%)
Blood and lymphatic system disorders
Splenomegaly	0/6 (0%)		1/8 (12.5%)
Thrombocytopenia	1/6 (16.7%)		0/8 (0%)
Hyperbilirubinaemia	1/6 (16.7%)		0/8 (0%)
Cardiac disorders
Bradycardia	0/6 (0%)		1/8 (12.5%)
Endocrine disorders
Hypoglycaemia	0/6 (0%)		1/8 (12.5%)
Gastrointestinal disorders
Chronic gastrointestinal bleeding	1/6 (16.7%)		0/8 (0%)
Colonic obstruction	0/6 (0%)		1/8 (12.5%)
Diarrhoea	1/6 (16.7%)		0/8 (0%)
Gastrointestinal bleed	0/6 (0%)		1/8 (12.5%)
General disorders
Medical device complication	0/6 (0%)		1/8 (12.5%)
Hepatobiliary disorders
Hepatic lesion	1/6 (16.7%)		0/8 (0%)
Hepatic shock	0/6 (0%)		1/8 (12.5%)
Hepatomegaly	0/6 (0%)		1/8 (12.5%)
Infections and infestations
Septic shock	0/6 (0%)		1/8 (12.5%)
Sinusitis	0/6 (0%)		1/8 (12.5%)
Urosepsis	0/6 (0%)		1/8 (12.5%)
Vancomycin-resistant enterococcal infection	1/6 (16.7%)		0/8 (0%)
Investigations
Bilirubin elevated	1/6 (16.7%)		0/8 (0%)
Clostridium difficile toxin test positive	1/6 (16.7%)		0/8 (0%)
Elevated liver enzymes	0/6 (0%)		1/8 (12.5%)
Late diastolic murmur	1/6 (16.7%)		0/8 (0%)
Liver enzyme abnormal	0/6 (0%)		1/8 (12.5%)
Metabolism and nutrition disorders
Acidosis	0/6 (0%)		1/8 (12.5%)
Hypernatraemia	0/6 (0%)		1/8 (12.5%)
Hypophosphataemia	1/6 (16.7%)		0/8 (0%)
Lactic acidosis	1/6 (16.7%)		0/8 (0%)
Nervous system disorders
Unresponsive	0/6 (0%)		1/8 (12.5%)
Psychiatric disorders
Agitation	0/6 (0%)		1/8 (12.5%)
Mental status changes	0/6 (0%)		1/8 (12.5%)
Respiratory, thoracic and mediastinal disorders
Aspiration	0/6 (0%)		1/8 (12.5%)
Bronchoconstriction	1/6 (16.7%)		0/8 (0%)
Hypoxia	0/6 (0%)		1/8 (12.5%)
Pneumonia	1/6 (16.7%)		0/8 (0%)
Pneumonia due to pseudomonas	2/6 (33.3%)		0/8 (0%)
Skin and subcutaneous tissue disorders
Decubitus ulcer	0/6 (0%)		1/8 (12.5%)
Ecchymosis	0/6 (0%)		1/8 (12.5%)
Skin tear	1/6 (16.7%)		0/8 (0%)
Vascular disorders
Abdominal aortic aneurysm	1/6 (16.7%)		0/8 (0%)
Acute hypotension	1/6 (16.7%)		0/8 (0%)
Hypotension	1/6 (16.7%)		3/8 (37.5%)

Limitations/Caveats

This study was terminated early due to low participant enrollment.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission.