Short-Course Antibiotics for Childhood Pneumonia

(PRESTO-2 Trial)

Overseen By Shamini Selvakumar, MD

Age: < 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Jeffrey Pernica

Must not be taking: Coumadin, Tetracyclines

Disqualifiers: Chronic lung disease, Congenital heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8-10 days

75 Participants Needed

Trial Summary

What is the purpose of this trial?

Children are commonly hospitalized because of community-acquired pneumonia (CAP). There are multiple high-quality randomized trials of short-course antibiotic therapy (3-5 days of treatment) for adults hospitalized with CAP - but there is very little evidence in children. We intend to do a pilot RCT of short-course (3-5 days) vs standard-duration (8-10 days) antibiotic therapy for children hospitalized for CAP.

Will I have to stop taking my current medications?

The trial requires that children stop taking coumadin-based anticoagulants and tetracycline-type antibiotics due to potential interactions with the study medication, amoxicillin.

What data supports the effectiveness of the drug Amoxicillin for treating childhood pneumonia?

Research shows that Amoxicillin is recommended by the World Health Organization as the best first-line treatment for non-severe childhood pneumonia, given twice daily for 3-5 days. Additionally, a study found no significant difference in effectiveness between Amoxicillin and another antibiotic, co-trimoxazole, for treating non-severe pneumonia in children. ^{1 2 3 4 5}

Is amoxicillin safe for treating childhood pneumonia?

Research shows that amoxicillin is generally safe for treating childhood pneumonia, with few serious side effects. Some children experienced issues like recurrent pneumonia or stomach problems, but these were not common and were not directly linked to the length of amoxicillin treatment. ^{1 2 6 7 8}

How is the drug amoxicillin unique in treating childhood pneumonia?

Amoxicillin is unique in treating childhood pneumonia because it can be effectively used in a shorter 3-day course, which may lower costs, improve patient compliance, and help reduce antibiotic resistance compared to longer treatments. ^{1 2 5 9 10}

Eligibility Criteria

This trial is for children hospitalized with community-acquired pneumonia (CAP) who show signs like fast breathing, coughing, and increased effort to breathe. They must have physical exam findings that match CAP. Children without these specific symptoms or other criteria will not be eligible.

Inclusion Criteria

My child has severe pneumonia, confirmed by a doctor and abnormal chest images.

I have symptoms like rapid breathing, coughing, or difficulty breathing that suggest pneumonia.

Exclusion Criteria

I have used supplemental oxygen or had a fever in the last 24 hours.

I have a long-term lung condition.

I was diagnosed with a lung abscess in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either short-course (3-5 days) or standard-duration (8-10 days) antibiotic therapy for community-acquired pneumonia

8-10 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of late clinical response and development of complicated pneumonia

30 days

Treatment Details

Interventions

• Amoxicillin

Trial Overview The study is testing if a short course of antibiotics (3-5 days) is as effective as the standard longer treatment (8-10 days) in children with CAP. Some kids will get Amoxicillin while others may receive a placebo to compare outcomes.

Participant Groups

Group I: Short-course treatment Experimental Treatment 1 Intervention

5 days of placebo (after participants already received 3-5 days of antibiotics)

Group II: Standard-duration treatment Active Control 1 Intervention

5 days of amoxicillin (after participants already received 3-5 days of antibiotics)

Amoxicillin is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Amoxicillin for:

• Bacterial infections
• Respiratory tract infections
• Urinary tract infections
• Skin and soft tissue infections
• Ear, nose and throat infections

Approved in United States as Amoxicillin for:

• Infections of the ear, nose, throat, genitourinary tract, skin and skin structure, and lower respiratory tract

Approved in Canada as Amoxicillin for:

• Bacterial infections
• Respiratory tract infections
• Urinary tract infections
• Skin and soft tissue infections

Who Is Running the Clinical Trial?

Jeffrey Pernica

Lead Sponsor

Trials

3

Recruited

230+

Jeffrey

Lead Sponsor

Trials

2

Recruited

150+

Findings from Research

In a study involving 1471 children with non-severe pneumonia, both twice-daily oral co-trimoxazole and amoxicillin were found to be equally effective, with treatment failure rates of 16.1% for amoxicillin and 18.9% for co-trimoxazole.

The study highlights the importance of monitoring patients closely, especially infants with a history of breathing difficulties or prolonged illness, to prevent worsening conditions, as these factors were linked to higher treatment failure rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of co-trimoxazole versus amoxicillin twice daily for treatment of pneumonia: a randomised controlled clinical trial in Pakistan. [2019]

In a study of 204 children aged 0-5 years with non-severe pneumonia, amoxicillin showed a significantly lower treatment failure rate (8.09%) compared to co-trimoxazole (39.05%), indicating that amoxicillin is more effective for this condition.

Although amoxicillin is more effective, it is also more expensive (2.3 times higher cost) and has slightly lower compliance rates (83.84% for amoxicillin vs. 90.47% for co-trimoxazole), suggesting a need for better patient counseling to improve adherence to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Effectiveness of Co-trimoxazole vs. Amoxicillin in the Treatment of Non-Severe Pneumonia in Children in India: A Randomized Controlled Trial. Rajesh, SM., Singhal, V.[2021]

In a study of 100 children with bacterial pneumonia, those treated with amoxycillin plus clavulanic acid showed significantly better improvement in symptoms like chest pain and fever by Day 3 compared to those treated with amoxycillin alone.

The combination treatment had a higher overall clinical efficacy rate of 93.8%, compared to 60.4% for amoxycillin alone, with only two mild adverse reactions reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open, comparative evaluation of amoxycillin and amoxycillin plus clavulanic acid ('Augmentin') in the treatment of bacterial pneumonia in children. Jibril, HB., Ifere, OA., Odumah, DU.[2019]

The WHO has updated its recommendations for treating non-severe childhood pneumonia, emphasizing the use of amoxicillin as the first-line treatment for bacterial causes like Streptococcus pneumoniae and Haemophilus influenzae, based on a review of current literature.

Treatment failure should be monitored closely, defined as a lack of improvement after 48-72 hours, and if it occurs, alternative diagnoses and adherence to therapy should be investigated, with high-dose amoxicillin-clavulanic acid as a potential second-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recommendations for treatment of childhood non-severe pneumonia. Grant, GB., Campbell, H., Dowell, SF., et al.[2022]

In a trial involving 2009 children aged 2-59 months with non-severe pneumonia, both 3 days of oral amoxycillin and 5 days of co-trimoxazole showed similar effectiveness, with no significant difference in clinical failure rates.

The study demonstrated good adherence and low loss to follow-up, reinforcing the reliability of the findings that neither antibiotic was superior in treating non-severe pneumonia in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of 3-day amoxycillin vs. 5-day co-trimoxazole in the treatment of non-severe pneumonia in children aged 2-59 months of age: a multi-centric open labeled trial. Awasthi, S., Agarwal, G., Singh, JV., et al.[2015]

In a trial involving 1126 HIV-negative children aged 2-59 months with fast breathing pneumonia, amoxicillin treatment was found to be well tolerated, with only 10.9% of serious adverse events (SAEs) in the amoxicillin group possibly related to the medication.

No life-threatening pneumonia SAEs or deaths occurred in either the amoxicillin or placebo groups, indicating that amoxicillin is a safe option for treating fast breathing pneumonia in young children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of serious adverse events in a paediatric fast breathing pneumonia clinical trial in Malawi. Nkwopara, E., Schmicker, R., Mvalo, T., et al.[2020]

A study involving 3000 children with non-severe chest-indrawing pneumonia in Malawi found that both 3-day and 5-day amoxicillin treatments were effective, with no significant differences in treatment failure or serious adverse events (SAEs) between the two durations.

The trial indicated that while male and younger children experienced more SAEs, overall, amoxicillin was safe for treating pneumonia in children, with very few SAEs attributed to the medication itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of serious adverse events in a pediatric community-acquired pneumonia randomized clinical trial in Malawi. Ginsburg, AS., May, S.[2022]

In a study involving 399 adults with community-acquired pneumonia, pristinamycin (PRI) was found to be clinically as effective as amoxicillin (AMX), with an 87.6% success rate in both treatment groups.

Both PRI and AMX had similar safety profiles, with no serious adverse events related to the study drugs, indicating that PRI is a well-tolerated alternative for treating bacterial pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of pristinamycin vs amoxicillin in community acquired pneumonia in adults]. Trémolières, F., Mayaud, C., Mouton, Y., et al.[2013]

In a study involving 134 Gambian children under 5 with severe pneumonia, treatment with oral co-trimoxazole for 5 days showed no significant difference in outcomes compared to a single dose of procaine penicillin and 5 days of oral ampicillin.

Co-trimoxazole is a cost-effective alternative, requiring less frequent dosing and simpler administration, making it a suitable first-choice antibiotic for treating pneumonia in young children in developing countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial of co-trimoxazole versus procaine penicillin with ampicillin in treatment of community-acquired pneumonia in young Gambian children. Campbell, H., Byass, P., Forgie, IM., et al.[2019]

A study involving 2000 children with non-severe pneumonia found that a 3-day course of oral amoxicillin is just as effective as a 5-day course, with similar rates of treatment failure (21% vs. 20%).

The main factor leading to treatment failure was non-compliance, highlighting the importance of ensuring children complete their prescribed antibiotic course, regardless of whether it is for 3 or 5 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of 3 days versus 5 days of oral amoxicillin for treatment of childhood pneumonia: a multicentre double-blind trial. [2015]

References

1. England pubmed.ncbi.nlm.nih.gov

Clinical efficacy of co-trimoxazole versus amoxicillin twice daily for treatment of pneumonia: a randomised controlled clinical trial in Pakistan. [2019]

2. Iran pubmed.ncbi.nlm.nih.gov

Clinical Effectiveness of Co-trimoxazole vs. Amoxicillin in the Treatment of Non-Severe Pneumonia in Children in India: A Randomized Controlled Trial. [2021]

3. England pubmed.ncbi.nlm.nih.gov

An open, comparative evaluation of amoxycillin and amoxycillin plus clavulanic acid ('Augmentin') in the treatment of bacterial pneumonia in children. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Recommendations for treatment of childhood non-severe pneumonia. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Effectiveness of 3-day amoxycillin vs. 5-day co-trimoxazole in the treatment of non-severe pneumonia in children aged 2-59 months of age: a multi-centric open labeled trial. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Analysis of serious adverse events in a paediatric fast breathing pneumonia clinical trial in Malawi. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Analysis of serious adverse events in a pediatric community-acquired pneumonia randomized clinical trial in Malawi. [2022]

8. France pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of pristinamycin vs amoxicillin in community acquired pneumonia in adults]. [2013]

9. England pubmed.ncbi.nlm.nih.gov

Trial of co-trimoxazole versus procaine penicillin with ampicillin in treatment of community-acquired pneumonia in young Gambian children. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Clinical efficacy of 3 days versus 5 days of oral amoxicillin for treatment of childhood pneumonia: a multicentre double-blind trial. [2015]