Safety and Efficacy of Thymic Peptides in the Treatment of Hospitalized COVID-19 Patients in Honduras

• ClinicalTrials.gov Identifier: NCT04771013
• Recruitment Status: Completed
• First Posted: February 25, 2021
• Results First Posted: February 4, 2022
• Last Update Posted: February 4, 2022
• Sponsor: Universidad Católica de Honduras
• Collaborator: Pontificia Universidad Catolica de Chile
• Information provided by (Responsible Party): Héctor Miguel Ramos Zaldívar, Universidad Católica de Honduras

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: COVID-19
• Intervention: Biological: Thymic peptides
• Enrollment: 22

Participant Flow

Recruitment Details

Pre-assignment Details

22 participants were enrolled in the intervention group. A participant-level comparison based on a control group by propensity score matching from registry data was performed. This accounts for the 22 patients in the arm of the historic control group. ClinicalTrials.gov Identifier: NCT04771013 MedRxiv: A nonrandomized phase 2 trial of oral thymic peptides in hospitalized patients with Covid-19. doi: https://doi.org/10.1101/2021.12.05.21267318

Arm/Group Title	Daily Oral Dose of Thymic Peptides	Historic Control Group
Arm/Group Description	Patients will receive a daily oral dose of 250 mg of lyophilized thymic peptides dissolved in 50 mL of water (one hour before or two hours after a meal) in addition to the standard treatment, for up to 20 days or until medical discharge. Thymic peptides: 250 mg oral daily dose of lyophilized thymic peptides dissolved in 50 mL of water, administered with an empty stomach.	A participant-level comparison based on a control group by propensity score matching from registry data was performed. For the comparison group, registry data from June 2020 to February 2021 was considered, as standardization of Stage IIB therapeutic management to its current guideline in Honduras occurred on May 2020. Although highly controversial among the Honduran scientific community, guidelines approved by the Honduran Ministry of Health for the treatment of Covid-19 include the use of ivermectin, azithromycin, zinc, hydroxychloroquine or chloroquine, acetaminophen, ibuprofen, and oral disinfectants (sodium hypochlorite, hypochlorous acid, hydrogen peroxide, among others) for the initial phases of disease progression. On top of these, therapeutic options for patients presenting with pulmonary compromise before or during hospitalization for phase IIb include colchicine, dexamethasone or methylprednisolone, and anticoagulation (rivaroxaban, apixaban, heparin, or enoxaparin).
Period Title: Overall Study
Started	22	22
Completed	20	16
Not Completed	2	6
Reason Not Completed
Withdrawal by Subject	2	0
Death	0	5
Referred to another hospital before day 20	0	1

Baseline Characteristics

Arm/Group Title		Daily Oral Dose of Thymic Peptides	Historic Control Group	Total
Arm/Group Description		Patients will receive a daily oral dose of 250 mg of lyophilized thymic peptides dissolved in 50 mL of water (one hour before or two hours after a meal) in addition to the standard treatment, for up to 20 days or until medical discharge. Thymic peptides: 250 mg oral daily dose of lyophilized thymic peptides dissolved in 50 mL of water, administered with an empty stomach.	A participant-level comparison based on a control group by propensity score matching from registry data was performed. For the comparison group, registry data from June 2020 to February 2021 was considered, as standardization of Stage IIB therapeutic management to its current guideline in Honduras occurred on May 2020. Although highly controversial among the Honduran scientific community, guidelines approved by the Honduran Ministry of Health for the treatment of Covid-19 include the use of ivermectin, azithromycin, zinc, hydroxychloroquine or chloroquine, acetaminophen, ibuprofen, and oral disinfectants (sodium hypochlorite, hypochlorous acid, hydrogen peroxide, among others) for the initial phases of disease progression. On top of these, therapeutic options for patients presenting with pulmonary compromise before or during hospitalization for phase IIb include colchicine, dexamethasone or methylprednisolone, and anticoagulation (rivaroxaban, apixaban, heparin, or enoxaparin).	Total of all reporting groups
Overall Number of Baseline Participants		22	22	44
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	22 participants	22 participants	44 participants
		52 (16)	57 (17)	54 (16)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	22 participants	22 participants	44 participants
≤60 years		15 68.2%	12 54.5%	27 61.4%
61-64 years		2 9.1%	3 13.6%	5 11.4%
≥ 65 years		5 22.7%	7 31.8%	12 27.3%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	22 participants	44 participants
	Female	7 31.8%	9 40.9%	16 36.4%
	Male	15 68.2%	13 59.1%	28 63.6%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Mestizo	Number Analyzed	22 participants	22 participants	44 participants
		22 100.0%	22 100.0%	44 100.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Honduras	Number Analyzed	22 participants	22 participants	44 participants
		22	22	44
Median no. of days since symptom onset; Median (Inter-Quartile Range); Unit of measure: Days
	Number Analyzed	22 participants	22 participants	44 participants
		11.5; (9 to 13)	10; (9 to 14)	10.5; (9 to 13)
Comorbidities; Mean (Standard Deviation); Unit of measure: Comorbidities
	Number Analyzed	22 participants	22 participants	44 participants
		2 (1)	2 (2)	2 (1)
Coexisting conditions-Diabetes; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	22 participants	44 participants
		11 50.0%	3 13.6%	14 31.8%
Coexisting conditions-Hypertension; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	22 participants	44 participants
		7 31.8%	9 40.9%	16 36.4%
Coexisting conditions-Obesity; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	22 participants	44 participants
		2 9.1%	4 18.2%	6 13.6%
Coexisting conditions-Chronic obstructive pulmonary disease; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	22 participants	44 participants
		1 4.5%	1 4.5%	2 4.5%
Coexisting conditions-Heart Failure; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	22 participants	44 participants
		0 0.0%	1 4.5%	1 2.3%
Coexisting conditions-Organ damage (other than lung); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	22 participants	44 participants
		12 54.5%	15 68.2%	27 61.4%
WHO Clinical Progression Score of 5 at hospitalization [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	22 participants	44 participants
		22 100.0%	22 100.0%	44 100.0%
		[1] Measure Description: WHO Clinical Progression Scale: 0, uninfected; 1, asymptomatic, viral RNA detected; 2, symptomatic and independent; 3, symptomatic and assistance needed; 4, hospitalised, no oxygen therapy; 5, hospitalised, oxygen by mask or nasal prongs; 6, hospitalised, oxygen by non-invasive ventilation or high flow; 7, intubation and mechanical ventilation pO2/FiO2 ≥150 or SpO2/FiO2 ≥200; 8, mechanical ventilation pO2/FiO2 <150 (SpO2/FiO2 <200) or vasopressors; 9, mechanical ventilation, pO2/FiO2 <150 and vasopressors, dialysis, or ECMO (extracorporeal membrane oxygenation); 10, dead.
Heart rate distribution; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	22 participants	44 participants
	51-90 beats/min	14 63.6%	10 45.5%	24 54.5%
	91-110 beats/min	6 27.3%	10 45.5%	16 36.4%
	111-130 beats/min	2 9.1%	2 9.1%	4 9.1%
Systolic blood pressure distribution 90-219 mmHg; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	22 participants	44 participants
		22 100.0%	22 100.0%	44 100.0%
Respiratory rate distribution; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	22 participants	44 participants
	21-24 breaths/min	2 9.1%	3 13.6%	5 11.4%
	≥ 25 breaths/min	20 90.9%	19 86.4%	39 88.6%
Oxygen saturation distribution; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	22 participants	44 participants
	92-93%	3 13.6%	3 13.6%	6 13.6%
	≤91%	19 86.4%	19 86.4%	38 86.4%
Temperature distribution; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	22 participants	44 participants
	35.6-37.9 °C	19 86.4%	19 86.4%	38 86.4%
	38-39 °C	3 13.6%	2 9.1%	5 11.4%
	≥39.1 °C	0 0.0%	1 4.5%	1 2.3%
SARS-CoV-2 positive test result; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	22 participants	44 participants
		22 100.0%	22 100.0%	44 100.0%

Outcome Measures

1. Primary Outcome

Title	Time to Participant Recovery
Description	Measured in days to clinical recovery that will be defined as the first day, during the 20 days after enrollment, on which a patient met the criteria for category 1, 2, or 3 on the eight-category ordinal scale. The categories are as follows: 1, not hospitalized and no limitations of activities; 2, not hospitalized, with limitation of activities, home oxygen requirement, or both; 3, hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care; 4, hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (related to Covid-19 or to other medical conditions); 5, hospitalized, requiring any supplemental oxygen; 6, hospitalized, requiring noninvasive ventilation or use of high-flow oxygen devices; 7, hospitalized, receiving invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); and 8, death.
Time Frame	During hospitalization for up to 20 days.

Outcome Measure Data

Analysis Population Description

Analyses were performed according to the intention-to-treat principle.

Arm/Group Title	Daily Oral Dose of Thymic Peptides	Historic Control Group
Arm/Group Description:	Patients will receive a daily oral dose of 250 mg of lyophilized thymic peptides dissolved in 50 mL of water (one hour before or two hours after a meal) in addition to the standard treatment, for up to 20 days or until medical discharge. Thymic peptides: 250 mg oral daily dose of lyophilized thymic peptides dissolved in 50 mL of water, administered with an empty stomach.	A participant-level comparison based on a control group by propensity score matching from registry data was performed. For the comparison group, registry data from June 2020 to February 2021 was considered, as standardization of Stage IIB therapeutic management to its current guideline in Honduras occurred on May 2020. Although highly controversial among the Honduran scientific community, guidelines approved by the Honduran Ministry of Health for the treatment of Covid-19 include the use of ivermectin, azithromycin, zinc, hydroxychloroquine or chloroquine, acetaminophen, ibuprofen, and oral disinfectants (sodium hypochlorite, hypochlorous acid, hydrogen peroxide, among others) for the initial phases of disease progression. On top of these, therapeutic options for patients presenting with pulmonary compromise before or during hospitalization for phase IIb include colchicine, dexamethasone or methylprednisolone, and anticoagulation (rivaroxaban, apixaban, heparin, or enoxaparin).
Overall Number of Participants Analyzed	22	22
Median (95% Confidence Interval); Unit of Measure: days
	6; (3.981 to 8.019)	12; (9.023 to 14.977)

2. Primary Outcome

Title	Number of Participants With Treatment Related Adverse Events as Assessed by the Common Terminology Criteria for Adverse Events Version 5.0
Description	Number of participants who experience adverse events ≥ Grade 3, as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0).
Time Frame	Up to 20 days

Outcome Measure Data

Analysis Population Description

Only Treatment Related Adverse Event data related to mortality was collected from the Historic Control population.

Arm/Group Title	Daily Oral Dose of Thymic Peptides	Historic Control Group
Arm/Group Description:	Patients will receive a daily oral dose of 250 mg of lyophilized thymic peptides dissolved in 50 mL of water (one hour before or two hours after a meal) in addition to the standard treatment, for up to 20 days or until medical discharge. Thymic peptides: 250 mg oral daily dose of lyophilized thymic peptides dissolved in 50 mL of water, administered with an empty stomach.	A participant-level comparison based on a control group by propensity score matching from registry data was performed. For the comparison group, registry data from June 2020 to February 2021 was considered, as standardization of Stage IIB therapeutic management to its current guideline in Honduras occurred on May 2020. Although highly controversial among the Honduran scientific community, guidelines approved by the Honduran Ministry of Health for the treatment of Covid-19 include the use of ivermectin, azithromycin, zinc, hydroxychloroquine or chloroquine, acetaminophen, ibuprofen, and oral disinfectants (sodium hypochlorite, hypochlorous acid, hydrogen peroxide, among others) for the initial phases of disease progression. On top of these, therapeutic options for patients presenting with pulmonary compromise before or during hospitalization for phase IIb include colchicine, dexamethasone or methylprednisolone, and anticoagulation (rivaroxaban, apixaban, heparin, or enoxaparin).
Overall Number of Participants Analyzed	22	22
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	5 22.7%

3. Primary Outcome

Title	Number of Participants With Treatment Related Side Effects as Assessed by the General Assessment of Side Effects
Description	Number of participants who experience severe side effects as defined by the General Assessment of Side Effects (GASE).
Time Frame	Up to 20 days

Outcome Measure Data

Analysis Population Description

Treatment Related Side Effects data not collected from the Historic Control population.

Arm/Group Title	Daily Oral Dose of Thymic Peptides
Arm/Group Description:	Patients will receive a daily oral dose of 250 mg of lyophilized thymic peptides dissolved in 50 mL of water (one hour before or two hours after a meal) in addition to the standard treatment, for up to 20 days or until medical discharge. Thymic peptides: 250 mg oral daily dose of lyophilized thymic peptides dissolved in 50 mL of water, administered with an empty stomach.
Overall Number of Participants Analyzed	22
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%

4. Secondary Outcome

Title	Number of Participants That Died by Day 20
Description	Number of participants that died due to any reason by day 20.
Time Frame	Up to 20 days

Outcome Measure Data

Analysis Population Description

The analysis assessed the number of patients that died in each arm by day 20.

Arm/Group Title	Daily Oral Dose of Thymic Peptides	Historic Control Group
Arm/Group Description:	Patients will receive a daily oral dose of 250 mg of lyophilized thymic peptides dissolved in 50 mL of water (one hour before or two hours after a meal) in addition to the standard treatment, for up to 20 days or until medical discharge. Thymic peptides: 250 mg oral daily dose of lyophilized thymic peptides dissolved in 50 mL of water, administered with an empty stomach.	A participant-level comparison based on a control group by propensity score matching from registry data was performed. For the comparison group, registry data from June 2020 to February 2021 was considered, as standardization of Stage IIB therapeutic management to its current guideline in Honduras occurred on May 2020. Although highly controversial among the Honduran scientific community, guidelines approved by the Honduran Ministry of Health for the treatment of Covid-19 include the use of ivermectin, azithromycin, zinc, hydroxychloroquine or chloroquine, acetaminophen, ibuprofen, and oral disinfectants (sodium hypochlorite, hypochlorous acid, hydrogen peroxide, among others) for the initial phases of disease progression. On top of these, therapeutic options for patients presenting with pulmonary compromise before or during hospitalization for phase IIb include colchicine, dexamethasone or methylprednisolone, and anticoagulation (rivaroxaban, apixaban, heparin, or enoxaparin).
Overall Number of Participants Analyzed	22	22
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	5 22.7%

Adverse Events

Time Frame	Patients were evaluated daily during their hospitalization, from day 1 through 20. Patients who agreed to follow-ups by phone communication were monitored for adverse events or side effects up to two weeks after discharge.
Adverse Event Reporting Description	Adverse events ≥ Grade 3, as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0), were analyzed. Only Treatment Related Adverse Event data related to mortality was collected from the Historic Control population.
Arm/Group Title	Daily Oral Dose of Thymic Peptides		Historic Control Group
Arm/Group Description	Patients will receive a daily oral dose of 250 mg of lyophilized thymic peptides dissolved in 50 mL of water (one hour before or two hours after a meal) in addition to the standard treatment, for up to 20 days or until medical discharge. Thymic peptides: 250 mg oral daily dose of lyophilized thymic peptides dissolved in 50 mL of water, administered with an empty stomach.		A participant-level comparison based on a control group by propensity score matching from registry data was performed. For the comparison group, registry data from June 2020 to February 2021 was considered, as standardization of Stage IIB therapeutic management to its current guideline in Honduras occurred on May 2020. Although highly controversial among the Honduran scientific community, guidelines approved by the Honduran Ministry of Health for the treatment of Covid-19 include the use of ivermectin, azithromycin, zinc, hydroxychloroquine or chloroquine, acetaminophen, ibuprofen, and oral disinfectants (sodium hypochlorite, hypochlorous acid, hydrogen peroxide, among others) for the initial phases of disease progression. On top of these, therapeutic options for patients presenting with pulmonary compromise before or during hospitalization for phase IIb include colchicine, dexamethasone or methylprednisolone, and anticoagulation (rivaroxaban, apixaban, heparin, or enoxaparin).
All-Cause Mortality
	Daily Oral Dose of Thymic Peptides		Historic Control Group
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/22 (0.00%)		5/22 (22.73%)
Serious Adverse Events
	Daily Oral Dose of Thymic Peptides		Historic Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0.00%)		5/22 (22.73%)
Respiratory, thoracic and mediastinal disorders
Death due to respiratory failure *	0/22 (0.00%)	0	5/22 (22.73%)	5
* Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Daily Oral Dose of Thymic Peptides		Historic Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0.00%)		0/22 (0.00%)

Limitations and Caveats

Limitations of this study include its small sample size and the lack of a prospectively randomized control group. This was a single-center study that included only mestizo population, which might have impacted its universal validity.

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Héctor M. Ramos-Zaldívar
• Organization: GIMUNICAH
• Phone: +56934988958
• EMail: hramos@unicah.edu

• Responsible Party: Héctor Miguel Ramos Zaldívar, Universidad Católica de Honduras
• ClinicalTrials.gov Identifier: NCT04771013
• Other Study ID Numbers: AEC-01-2021; COM-2020-01 ( Other Identifier: Catholic University of Honduras IRB in Tegucigalpa ); AEC-01-2021 ( Registry Identifier: Dirección General de Vigilancia del Marco Normativo Honduras )
• First Submitted: February 24, 2021
• First Posted: February 25, 2021
• Results First Submitted: January 13, 2022
• Results First Posted: February 4, 2022
• Last Update Posted: February 4, 2022